<Page>

                                                                   EXHIBIT 10.35

    (WITH CERTAIN CONFIDENTIAL INFORMATION DELETED AND MARKED WITH BRACKETED
                                    ASTERIKS]


                           FIRST REVISED AND RESTATED
                    RESEARCH AND EARLY DEVELOPMENT AGREEMENT


                                     BETWEEN


                       VERTEX PHARMACEUTICALS INCORPORATED

                                       AND

                               NOVARTIS PHARMA AG

<Page>

                    Research and Early Development Agreement

                                TABLE OF CONTENTS

<Table>
<Caption>
                                                                                                     Page Number
<S>                                                                                                           <C>
INTRODUCTION...................................................................................................1
   ARTICLE I - DEFINITIONS.....................................................................................2
   ARTICLE II -- RESEARCH PROGRAM..............................................................................7
   2.1.   Commencement.........................................................................................7
   2.2.   Term.................................................................................................7
   2.3.   Research Diligence...................................................................................8
   2.4.   Research Plan........................................................................................8
   2.5.   Joint Research Committee.............................................................................8
   2.6.   Joint Steering Committee............................................................................10
   2.7.   Exchange of Information.............................................................................10
   2.8.   [This section has been intentionally left blank.]...................................................11
   2.9.   Exclusivity.........................................................................................11

ARTICLE III -- PAYMENTS.......................................................................................12
   3.1.   Signature Payment by NOVARTIS.......................................................................12
   3.2.   Staffing and Research Support Payments..............................................................12
   3.3.   Development Loan Facility...........................................................................13
   3.4.   Records.............................................................................................13

ARTICLE IV --  LICENSE, DEVELOPMENT AND COMMERCIALIZATION RIGHTS..............................................14
   4.1.   Development Election................................................................................14
   4.2.   [This section has been intentionally left blank.]...................................................16
   4.3.   Extension of Exercise Period........................................................................16
   4.4.   Refused Candidate...................................................................................16
   4.5.   Back-up Compounds...................................................................................17
   4.6.   [This section has been intentionally left blank.]...................................................19
   4.7.   Clinical Trial Material.............................................................................19
   4.8.   Special Provisions Regarding VX-680, VX-528 and VX-608..............................................19

ARTICLE V --   CONFIDENTIALITY................................................................................21
   5.1.   Undertaking.........................................................................................21
   5.2.   Exceptions..........................................................................................22
   5.3.   Publicity...........................................................................................23
   5.4.   Survival............................................................................................23

ARTICLE VI --  PUBLICATION....................................................................................23

ARTICLE VII -- INDEMNIFICATION................................................................................24
   7.1.   Indemnification by VERTEX...........................................................................24
   7.2.   Indemnification by NOVARTIS.........................................................................25
   7.3.   Claims Procedures...................................................................................25
   7.4.   Compliance..........................................................................................26

ARTICLE VIII --  PATENTABLE INVENTIONS........................................................................27
   8.1.   Ownership...........................................................................................27
   8.2.   Preparation.........................................................................................27
   8.3.   Costs...............................................................................................27
</Table>

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page i

<Page>

                    Research and Early Development Agreement

                                TABLE OF CONTENTS

<Table>
<Caption>
                                                                                                     Page Number
<S>                                                                                                           <C>
ARTICLE IX --  TERM AND TERMINATION...........................................................................28
   9.1.   Term................................................................................................28
   9.2.   Termination of the Research Program by NOVARTIS for Cause...........................................28
   9.3.   Termination of the Research Program by VERTEX for Cause.............................................29
   9.4.   [This section has been intentionally left blank.]...................................................29
   9.5.   Termination for Scientific Cause....................................................................29
   9.6.   Effect of Termination...............................................................................29

ARTICLE X --   REPRESENTATIONS AND WARRANTIES.................................................................30
   10.1.  Representations and Warranties of VERTEX............................................................30
   10.2.  Representations and Warranties of NOVARTIS..........................................................31

ARTICLE XI --  DISPUTE RESOLUTION.............................................................................31
   11.1.  Governing Law, and Jurisdiction.....................................................................31
   11.2.  Dispute Resolution Process..........................................................................32

ARTICLE XII -- MISCELLANEOUS PROVISIONS.......................................................................33
   12.1.  Official Language...................................................................................33
   12.2.  Waiver..............................................................................................33
   12.3.  Force Majeure.......................................................................................33
   12.4.  Severability........................................................................................33
   12.5.  Government Acts.....................................................................................33
   12.6.  Government Approvals................................................................................34
   12.7.  Export Controls.....................................................................................34
   12.8.  Assignment..........................................................................................34
   12.9.  Affiliates..........................................................................................34
   12.10. Counterparts........................................................................................35
   12.11. No Agency...........................................................................................35
   12.12. Notice..............................................................................................35
   12.13. Headings............................................................................................36
   12.14. Authority...........................................................................................36
   12.15. Entire Agreement....................................................................................36
   12.16. Standstill..........................................................................................36
   12.17. Notice of Pharmaceutical Side-Effects...............................................................37
   12.18. Inflation Adjustment................................................................................37
   12.19. Invoice Requirement.................................................................................38
   12.20. Hardship............................................................................................38

Exhibit A        Form of License, Development and Commercialization Agreement
Exhibit B        Form of Invoice
Schedule 1.13    Excluded Compounds and Excluded Kinases
Schedule 2.4.3   Development Candidate Criteria
</Table>

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page ii
<Page>

                           FIRST REVISED AND RESTATED

                    RESEARCH AND EARLY DEVELOPMENT AGREEMENT

     First Revised and Restated Agreement made this 3rd day of February, 2004,
(as so revised and restated, the "Research Agreement"), revising and restating
that certain Research And Early Development Agreement dated May 8, 2000 (the
"Original Agreement"), between VERTEX PHARMACEUTICALS INCORPORATED ("VERTEX"), a
Massachusetts corporation with principal offices at 130 Waverly Street,
Cambridge, MA 02139-4242, and NOVARTIS PHARMA AG ("NOVARTIS"), a Swiss
corporation with principal offices at Lichtstrasse 35, CH-4056 Basel,
Switzerland.

     This Research Agreement is intended by the parties to replace and supercede
the rights and obligations of the parties under the Original Agreement with
respect to the subject matter thereof, except that the terms of the Original
Agreement shall be deemed to govern the rights and obligations of the parties
with respect to the Compounds known as VX-680 and VX-528, subject to the
provisions of Section 4.8(b) of this Research Agreement.

                                  INTRODUCTION

     WHEREAS, VERTEX has undertaken a broad drug discovery program with the
objective of designing novel, small-molecule compounds targeting the kinase
protein super-family;

     WHEREAS, NOVARTIS is also interested in developing and commercializing
drugs targeting kinase proteins and has particular expertise in developing,
registering, manufacturing, marketing and selling pharmaceuticals worldwide;

     WHEREAS, both parties desire to revise and restate the Original Agreement
to reflect agreed modifications to the original collaboration, which involve
among other things a redirection of VERTEX's efforts from the delivery of
compounds which have progressed through early clinical testing, to the delivery
of Development Candidates, at an earlier stage in the development process, which
target selected Kinases and meet certain pre-agreed Development Candidate
Criteria; and

     WHEREAS, NOVARTIS may elect to develop, market and sell any or all of those
Compounds as drugs upon the terms set forth herein and in a License, Development
and Commercialization Agreement identical in substance to EXHIBIT A hereto;

     NOW THEREFORE, in consideration of the mutual covenants set forth in this
Research Agreement, and other good and valuable consideration, the parties agree
as follows:

                                    ARTICLE I
                                   DEFINITIONS

For purposes of this Agreement, the terms defined in this Article 1 shall have
the following meanings whether used in their singular or plural forms. Use of
the singular shall include the plural and vice versa, unless the context
requires otherwise:

                           First Revised and Restated
        Research and Early Development Agreement - Confidential - Page 1
<Page>

     1.1.      "AFFILIATE" shall mean, with respect to any Person, any other
Person which directly or indirectly, by itself or through one or more
intermediaries, controls, or is controlled by, or is under direct or indirect
common control with, such Person. The term "control" means the possession,
direct or indirect, of the power to direct or cause the direction of the
management and policies of a Person, whether through the ownership of voting
securities, by contract or otherwise. Control will be presumed if one Person
owns, either of record or beneficially, more than 50% of the voting stock of any
other Person. For the avoidance of any doubt, the Novartis Institute for
Functional Genomics, Inc. and The Friedrich Miescher Institute, as currently
operated, are not Affiliates of NOVARTIS for the purposes of this Research
Agreement.

               1.1.1.   "BACK-UP COMPOUND" shall mean, [***].

     1.2.      "BULK DRUG SUBSTANCE" shall mean a Drug Product Candidate in bulk
crystal, powder or other form suitable for incorporation in a Drug Product.

     1.3.               "COMPOUND" shall mean any chemical compound, including
salts thereof, which affects a Kinase and which was or is synthesized and/or
tested (including by screening) by or under the direction of VERTEX or its
Affiliates during the term of the Research Program conducted under this Research
Agreement, or was synthesized or tested by VERTEX or its Affiliates prior to the
Effective Date in a program targeted toward Kinase modulation.

     1.4.               "CONTROLLED" shall mean the legal authority or right of
a party hereto to grant a license or sublicense of intellectual property rights
to another party hereto, or to otherwise disclose proprietary or trade secret
information to such other party, without breaching the terms of any agreement
with a Third Party, infringing upon the intellectual property rights of a Third
Party, or misappropriating the proprietary or trade secret information of a
Third Party.

     1.5. (a)  "DEVELOPMENT CANDIDATE" shall mean a Compound that meets the
Development Candidate Criteria and which is either proposed by VERTEX, during
the term of the Research Program [***], for formal pre-clinical development, or
is selected by NOVARTIS on or before the Final Termination Date for formal
pre-clinical development pursuant to the provisions of Section 4.1 hereof.

     1.5. (b)  "DEVELOPMENT CANDIDATE INFORMATION" will mean all material
information known to VERTEX about a Development Candidate, including analytical
results and raw data, which NOVARTIS reasonably needs in order to decide whether
to exercise the Development Election with respect to the Development Candidate.
The Development Candidate Information shall include any previously undisclosed
information with respect to VERTEX Kinase Technology which is important to a
scientific and commercial evaluation of the Development Candidate. Development
Candidate Information will also include comparable information known to VERTEX
concerning all Compounds which are Back-up Compounds, as defined herein, to the
specific Development Candidate which is the subject of the Development Candidate
Information. [***]

     1.5.(c)   "DEVELOPMENT CANDIDATE CRITERIA" shall mean (a) the criteria
set forth on Schedule 2.4.3 hereof and (b) such further, more specific criteria
to be determined by the JRC as soon as possible after the start of each research
project with respect to each particular Kinase

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 2
<Page>

target, each therapeutic application, special delivery forms, and the like, as
set forth in Section 2.5.3 hereof.

     1.6.      "DEVELOPMENT ELECTION" shall have the meaning set forth in
Section 4.1 hereof.

     1.7.      "DEVELOPMENT PROGRAM" shall mean activities associated with
development of a Drug Product Candidate as specified in the License Agreement.

     1.8.      [This section has been intentionally left blank.]

     1.9.      "DRUG PRODUCT" shall mean a finished dosage form which is
prepared from Bulk Drug Substance and is ready for administration to the
ultimate consumer as a pharmaceutical.

     1.10. (a) "DRUG PRODUCT CANDIDATE" shall mean a Development Candidate
which has been selected by NOVARTIS for development and commercialization under
the License Agreement, pursuant to exercise of its Development Election under
Section 4.1 hereof.

     1.10. (b) "DRUG PRODUCT CANDIDATE BACKUP CANDIDATE" shall mean any
Back-up Compound for which NOVARTIS has exercised its Development Election under
Section 4.5 hereof.

     1.11.     [This section has been intentionally left blank.]

     1.12.     "EFFECTIVE DATE" shall mean the effective date of the Original
Agreement as set forth on the first page hereof.

     1.13.     "EXCLUDED COMPOUNDS" shall mean any chemical compounds the
therapeutic effect of which in humans is thought to be principally derived from
an effect on one or more Excluded Kinases. "Excluded Compounds" shall also
include the Compound known as [***]. An "analog" shall mean any compounds (or
salts thereof) which are claimed in [***] which NOVARTIS can demonstrate by
written record were synthesized by NOVARTIS before the Effective Date. "Excluded
Compounds" shall also include any Compounds directed toward modulation of a
Kinase which has been added to the list of Excluded Kinases by the operation of
Section 4.4 hereof; provided that in no event shall an Excluded Compound include
a Drug Product Candidate.

     1.14.     "EXCLUDED KINASES" shall mean the human kinases specifically
identified in Schedule 1.13 hereto. "Excluded Kinases" shall also include any
Kinase hereafter added to the list of Excluded Kinases pursuant to the
provisions of Section 4.4 hereof.

     1.15.     [This section has been intentionally left blank.]

     1.16.     "FIELD" shall mean the treatment or prevention of conditions or
diseases in humans, principally by affecting a Kinase other than an Excluded
Kinase.

     1.17.     "FINAL NOTICE PERIOD" shall have the meaning set forth in Section
4.1(d) hereof.

     1.17.1.   "FINAL REPORT" shall have the meaning set forth in Section 4.1(d)
hereof.

     1.17.2.   "FINAL REPORT PERIOD" shall have the meaning set forth in Section
4.1(d) hereof.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 3
<Page>

     1.17.3.   "FINAL TERMINATION DATE" shall have the meaning set forth in
Section 4.1(d) hereof.

     1.18.     "FTE" shall mean the equivalent of the work of one VERTEX
scientist or other project managerial professional, full time for one year,
which equates to a total of forty-seven (47) weeks or one thousand eight hundred
eighty (1880) hours per year of work, on or directly related to the Research
Program. Work in the Research Program can include, but is not limited to,
experimental laboratory work, project and research management, activities
directed toward evaluation of the commercial potential of a possible Drug
Candidate, recording and writing up results, reviewing literature and
references, holding scientific discussions, attending appropriate seminars and
symposia, and carrying out Joint Research Committee duties. FTE's shall include
equivalent scientific work in the Research Program delegated to and carried out
by contractors, under the general direction of VERTEX scientists; provided, that
the nature and quantity (as a percentage of total program FTE's) of the
delegated work shall not be such that the most substantial parts of the overall
Research Program, in terms of projected value creation, have been delegated to
Third Parties. FTE's which result from work delegated to and carried out by
contractors will be separately identified by VERTEX on its invoices provided to
NOVARTIS under Section 12.19 hereof.

     1.19.     [This section has been intentionally left blank.]

     1.20.     [This section has been intentionally left blank.]

     1.21.     "JOINT RESEARCH COMMITTEE" OR "JRC" shall have the meaning
ascribed to it in Section 2.5 of this Research Agreement.

     1.22.     "JOINT STEERING COMMITTEE" OR "JSC" shall have the meaning
ascribed to it in Section 2.6 of this Research Agreement.

     1.23.     "KINASE" shall mean a human enzyme that catalyzes the transfer of
a phosphate group from a nucleoside triphosphate to a protein.

     1.24.     "KINASE TECHNOLOGY" shall mean all data, technical information,
know-how, experience, inventions (whether or not patented) trade secrets,
processes and methods discovered, developed or applied (with the consent of its
owner) and Controlled by either party or its Affiliates, in connection with
performance by either party under the Research Program, or in connection with
the conduct of a Development Program under the License Agreement prior to
termination of the Research Program, that relate to the research, development,
utilization, manufacture or use of Compounds, Development Candidates, Drug
Product Candidates or Drug Products (other than any such technology which is
exclusive to Excluded Kinases); provided, however, that the term Kinase
Technology shall not apply to VERTEX's general drug design technology whether in
hardware or software form, tangible or intangible.

     1.25.     "KNOW-HOW" means all Kinase Technology other than inventions
which are the subject of Patents; and "LEAD PERIOD" shall have the meaning set
forth in Section 4.5(a) hereof.

     1.26.     "LICENSE AGREEMENT" shall mean the License, Development and
Commercialization Agreement, identical in substance to EXHIBIT A to this
Research Agreement, to be executed by VERTEX and NOVARTIS with respect to each
Drug Product Candidate; and "NOTICE PERIOD" shall have the meaning set forth in
Section 4.1(b) hereof.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 4
<Page>

     1.27.     "NOVARTIS KNOW-HOW" shall mean all Know-How of NOVARTIS.

     1.28.     "NOVARTIS PATENTS" shall mean any Patents controlled by NOVARTIS
or its Affiliates claiming Kinase Technology.

     1.29.     "NOVARTIS KINASE TECHNOLOGY" shall mean all NOVARTIS Patents and
NOVARTIS Know-How.

     1.30.     "PATENTS" means all existing patents and patent applications and
all patent applications hereafter filed, including any continuation,
continuation-in-part, division, provisional or any substitute applications, any
patent issued with respect to any such patent applications, any reissue,
reexamination, renewal or extension (including any supplementary protection
certificate) of any such patent, and any confirmation patent or registration
patent or patent of addition based on any such patent, and all foreign
counterparts of any of the foregoing.

     1.31.     "PERSON" means any individual, corporation, partnership,
association, joint-stock company, trust, unincorporated organization or
government or political subdivision thereof.

     1.32.     [This section has been intentionally left blank.]

     1.33.     [This section has been intentionally left blank.]

     1.34.     "REFUSED CANDIDATE" shall have the meaning set forth in Section
4.4 hereof.

     1.35.     "REPLACEMENT CANDIDATE" shall have the meaning set forth in
Section 4.5(b) hereof.

     1.36.     "RESEARCH PLAN" shall have the meaning set forth in Section 2.4.1
hereto.

     1.37. (a) "RESEARCH PROGRAM" shall mean all research activities
undertaken under this Research Agreement associated with the identification and
design of Compounds and Development Candidates as provided herein; including but
not limited to identification and initial testing of Compounds; the conduct of
activities referenced in the Development Candidate Criteria with respect to
Compounds; and selection of Development Candidates from Compounds.

     1.37. (b) "RESEARCH TERMINATION DATE" shall mean the earlier of April
30, 2006 or the date upon which the Research Program is terminated under
Sections 9.2, 9.3 or 9.5 hereof.

     1.38.     "RESEARCH YEAR" means a twelve-month period during the term of
the Research Program commencing on May 1, and ending on April 30 of each year.
The first Research Year hereunder shall be deemed to have commenced on May 1,
2000.

     1.39.     [This space has been intentionally left blank.]

     1.40.     "TECHNOLOGY" shall mean NOVARTIS Kinase Technology and VERTEX
Kinase Technology.

     1.41.     "THIRD PARTY" shall mean any person or entity which is not a
party or an Affiliate of any party to this Research Agreement.

     1.42.     "THIRD PARTY REFERRAL" shall mean the procedure for resolution of
certain disputes hereunder which is set forth in Section 11.2(b) hereof.

     1.43.     "VERTEX KNOW-HOW" shall mean all Know-How of VERTEX.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 5
<Page>

     1.44.     "VERTEX PATENTS" shall mean any Patents Controlled by VERTEX or
its Affiliates claiming Kinase Technology.

     1.45.     "VERTEX KINASE TECHNOLOGY" shall mean all VERTEX Patents and
VERTEX Know-How.

Capitalized terms used but not otherwise defined herein which are defined in the
License Agreement shall have the meaning ascribed to them therein.

                                   ARTICLE II
                                RESEARCH PROGRAM

     2.1.          COMMENCEMENT.
            The Research Program originally commenced on May 1, 2000. VERTEX has
principal responsibility for the conduct of the Research Program and NOVARTIS
provides consultation, advice and such research effort as may be deemed
appropriate by the JRC and accepted by NOVARTIS. The JRC shall review and
coordinate all of the parties' efforts with respect to the Research Program.

     2.2.          TERM.
            The Research Program will conclude on May 1, 2006, unless earlier
terminated in accordance with the provisions hereof. At the request of either
party made during the fourth Research Year, the parties will discuss whether,
and upon what basis, the Research Program might be extended on comparable terms
beyond its initial 6 year term.

     2.3.          RESEARCH DILIGENCE.
            The common objective of the parties is to identify Development
Candidates as soon as practicable for selection by NOVARTIS as Drug Product
Candidates and for worldwide development and marketing under the terms of the
License Agreement. VERTEX will work diligently and use all reasonable efforts,
consistent with prudent business judgment, to identify Development Candidates
for acceptance by NOVARTIS as Drug Product Candidates. VERTEX intends to
dedicate to the Research Program at least that level of staffing referenced in
Section 3.2 hereof, and expects to employ an optimal combination of experience
and training in the Field. As a matter of corporate strategy, VERTEX has chosen
to dedicate a significant amount of its overall research efforts to work in the
Field, and will not change that overall strategy during the term of the Research
Program without prior notice to and approval by NOVARTIS.

     2.4.          RESEARCH PLAN; EARLY DEVELOPMENT PLAN.
            2.4.1. General. VERTEX originally prepared an overall research
plan for the Research Program which it submitted to the JRC for its review and
comment at the first meeting of the JRC after the Effective Date. The research
plan has been and will be revised, updated and submitted to the JRC at least
annually for its review and comment (as so revised, updated and submitted, the
"Research Plan").

            2.4.2. [This section has been intentionally left blank.]

            2.4.3. Plan Review. In developing the Research Plan, VERTEX
will take into account the intention of the parties to produce Compounds which
meet the Development

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 6
<Page>

Candidate Criteria. VERTEX shall not perform any work under this Research
Agreement with respect to Excluded Compounds or Excluded Kinases. The Research
Plan will be reviewed as necessary at each meeting of the JRC, and at any other
time upon the request of either party, and shall be modified as appropriate to
reflect material scientific or commercial developments. Any disagreements among
the parties with respect to these matters may be referred by either party to the
Joint Steering Committee for resolution. Notwithstanding the foregoing, VERTEX
shall have the final say with respect to the Research Plan.

     2.5.          JOINT RESEARCH COMMITTEE.
            2.5.1. Composition and Purposes. VERTEX and NOVARTIS have
established and will continue to participate in a Joint Research Committee
("JRC") consisting of at least eight (8) representatives (as may be increased or
decreased by the JRC), half of whom shall be designated from time to time by
each party. If the JRC chooses to designate a Committee Chair, the Chair will be
appointed from among the members of the Committee designated by VERTEX. The JRC
shall meet formally at least quarterly, or with such other frequency, and at
such time and location, as may be established by the Committee, for the
following purposes:

                     (i)   To receive and review reports by VERTEX and its
project teams, which shall be prepared and submitted to the JRC on a quarterly
basis within fifteen (15) days after the end of each calendar quarter, such
reports summarizing progress during the preceding quarter under the Research
Plan; and to review information with respect to the Compounds under
investigation (which VERTEX shall provide in form and content at least as
extensive as customarily provided to the JRC under the Original Agreement);

                     (ii)  To review a proposal by either party that specified
Excluded Compounds or Excluded Kinases be included in the Research Program, or
that a Kinase be added to the list of Excluded Kinases; provided that the JRC
shall have no authority to include or exclude any Compound or Kinase from the
Research Program, and that any such action must be the subject of a formally
adopted amendment to this Research Agreement;

                     (iii) To define as soon as possible the further, more
specific Development Criteria (x) for ongoing projects, after the signature of
this Research Agreement, or (y) for new projects, after the start of such new
research project;

                     (iv)  To review Development Candidates proposed by VERTEX
and to assess whether a given Development Candidate proposed by VERTEX meets the
Development Criteria;

                     (v)   To review the Research Plan and any proposed
revisions thereto;

                     (vi)  [This subsection has been intentionally left blank.];
and

                     (vii) To discuss matters relating to Patents, as may be
presented to the JRC by VERTEX or NOVARTIS.

            The party hosting a particular JRC meeting shall prepare and deliver
to the members of the JRC, within thirty (30) days after the date of each
meeting, minutes of such

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 7
<Page>

meeting setting forth, INTER ALIA, all decisions of the JRC, and including a
report on the progress of work performed. In case the JRC meets by means of
telephone or video conferences, this responsibility shall lie with VERTEX.

            2.5.2. Decision-Making.

                     (i)   Each of VERTEX and NOVARTIS shall have one vote on
the JRC. The objective of the JRC shall be to reach agreement by consensus on
all matters within the scope of the Research Plan. However, in the event of a
deadlock with respect to any action (which shall be deemed to have occurred if
either party shall request a vote of the JRC on a matter and that vote shall
either not be taken within thirty (30) days of the request or if taken shall
result in a tie vote) and subject to the procedure set forth in subsection (ii)
below as to certain matters, the vote of VERTEX, rendered after reasonable and
open discussion among the members of the JRC, shall be final and controlling.

                     (ii)  Notwithstanding the foregoing, with respect to JRC
decisions (x) as to the nature and extent of any additional Development
Candidate Criteria referenced in Section 2.5.3 hereof, any disagreement between
the parties that cannot be resolved within forty-five (45) days by the JRC (as
that period may be extended under (iii) below) shall be referred to the JSC for
resolution and if not resolved within seven (7) business days after referral,
shall be referred for final resolution in good faith by the Chief Executive
Officer of VERTEX and the Chief Executive Officer of NOVARTIS, and failing final
resolution, there will be no change to the Development Candidate Criteria; or
(y) as to whether or not Development Candidate Information provided by VERTEX,
pursuant to subsection (iii) below, is complete or as to whether or not a given
Compound proposed by VERTEX as a Development Candidate meets the Development
Criteria, the matter shall be referred as provided in subsection (x) above to
the JRC and the JSC and, failing agreement, the matter shall be referred for
final resolution under the provisions of Section 11.2(b) of this Research
Agreement.

                     (iii) In the event that NOVARTIS's representatives on the
JRC reasonably believe that the Development Candidate Information with respect
to a particular Development Candidate proposed by VERTEX to the JRC is
incomplete, NOVARTIS shall provide written notice thereof to VERTEX within
fifteen (15) business days after receipt of the Development Candidate
Information, and VERTEX shall undertake reasonable efforts to furnish the
requested additional Development Candidate Information within fifteen (15)
business days after receipt of NOVARTIS's notice hereunder. The 45-day period
provided for action by the JRC under subsection (ii) above shall be extended by
the amount of time required for VERTEX to provide the requested information, but
in any event not in excess of thirty (30) days.

                     (iv)  Notwithstanding any of the foregoing, if VERTEX and
NOVARTIS deadlock on any other matters being considered by the JRC which might
have a significant impact on the time or likely success of the Research Program,
the matter shall be referred to the JSC for resolution in accordance with
Section 2.6 hereof.

                     (v)   Each party shall retain the rights, powers, and
discretion granted to it under this Research Agreement, and the JRC shall not be
delegated or vested with any such rights, powers or discretion except as
expressly provided in this Research Agreement.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 8
<Page>

The JRC shall not have the power to amend or modify this Research Agreement,
which may only be amended or modified as provided in Section 12.15.

            2.5.3. ADDITIONAL DEVELOPMENT CANDIDATE CRITERIA. The parties
acknowledge that it may be necessary or appropriate to adopt additional
Development Candidate Criteria which more specifically define the
pre-development characteristics of Compounds which the parties believe may be
suitable for development and commercialization under the License Agreement,
based upon the Kinase targeted by a specific project under the Research Program
and the particular disease indication or indications thought to be addressed by
Compounds modulating the Kinase which is the subject of that project. [***] Any
disagreements with respect to the selection of additional Development Candidate
Criteria hereunder will be addressed as provided in Section 2.5.2(ii).

     2.6.          JOINT STEERING COMMITTEE.
            2.6.1. Composition and Purposes. VERTEX and NOVARTIS have
established and will continue to participate in a Joint Steering Committee
("JSC") which shall consist of an equal number of senior executives as may be
designated by each party from time to time. The JSC shall initially have four
(4) members. If the JSC chooses to designate a Committee Chair, the Chair will
be appointed from among the members of the JSC designated by NOVARTIS. The JSC
shall meet annually, or with such other frequency, and at such time and
location, as may be established by the Committee, for the following purposes:

                     (i)   General oversight of the entire collaboration between
VERTEX and NOVARTIS, including the Research Program and any development and
commercialization of a Drug Product Candidate under the License Agreement;

                     (ii)  Periodically review the overall goals and strategy of
the Research Program;

                     (iii) Discuss and attempt to resolve any deadlocked issues
submitted to it by the JRC, although the vote of VERTEX's representatives shall
prevail if the JSC is unable to reach a consensus on any matter other than
matters submitted to the JSC under Section 2.5.2(ii).

     2.7.          EXCHANGE OF INFORMATION.
            2.7.1. VERTEX, and at its sole discretion NOVARTIS, will share
information with the JRC, as soon as it is available, necessary to facilitate
mutual understanding of the status of the Research Program and decision-making
in connection therewith.

            2.7.2. Neither VERTEX nor NOVARTIS shall use Kinase Technology
disclosed by the other party (excluding information which is no longer subject
to confidentiality restrictions under Article V by reason of the exceptions set
forth in Section 5.2) for any purpose, including the filing of patent
applications containing such information, without the other party's consent,
other than for carrying out the Research Program or discharging its
responsibilities under the License Agreement, or as otherwise permitted under
the Research Agreement or the License Agreement.

            2.7.3. [This section has been intentionally left blank.]

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 9
<Page>

            2.7.4. [***]

     2.8.          [This section has been intentionally left blank.]

     2.9.          FREEDOM-OF-ACTION AND EXCLUSIVITY

            2.9.1. [***]

            2.9.2. [***]

            2.9.3. [This section has been intentionally left blank.]

            2.9.4. [This section has been intentionally left blank.]

            2.9.5. [This section has been intentionally left blank.]

            2.9.6. [This section has been intentionally left blank.]

                                   ARTICLE III
                                    PAYMENTS

     3.1.          SIGNATURE PAYMENT BY NOVARTIS.
            Upon the Effective Date of this Research Agreement NOVARTIS made an
initial non-refundable payment of $15,000,000 to VERTEX.

     3.2.          STAFFING AND RESEARCH SUPPORT PAYMENTS.
            NOVARTIS has made or will make the payments specified below to
VERTEX during each Research Year in support of the Research Program under this
Research Agreement. The required payments are based upon the following
assumptions: (a) the average number of FTE's which VERTEX will have employed in
the Research Program during a Research Year will be approximately equal to the
FTE Level listed in the third column below; and (b) the annual rate per FTE is
approximately [***]. If the average FTE level for any Research Year is less than
the level specified below for that year (the difference being referred to in
this section as an "FTE Shortfall"), then the amount of funding specified below
for that Research Year shall be reduced by an amount (the "FTE Shortfall
Amount") which bears the same relation to the total funding specified below for
that Research Year as the FTE Shortfall bears to the projected FTE Level for
that Year. The FTE Shortfall Amount shall be carried over from year to year and
applied to compensate VERTEX for FTE Levels in subsequent Research Years which
exceed the level for those Years as specified below. In any such subsequent
Research Year, VERTEX shall be entitled to receive out of any remaining FTE
Shortfall Amount a payment equal to the value (computed with reference to the
inflation-adjusted FTE rate specified above) of any FTE's actually employed
during that Research Year in excess of the FTE Level specified for that year
("Excess FTE's"). Notwithstanding the foregoing, the FTE Shortfall Amount will
not be applied to compensate VERTEX on account of more than 20 Excess FTE's in
any one Research Year.

<Table>
<Caption>
       RESEARCH YEAR                    FUNDING                 FTE LEVEL
             <S>                         <C>                      <C>
             1                           [***]                    [***]
             2                           [***]                    [***]
             3                           [***]                    [***]
</Table>

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 10
<Page>

<Table>
<Caption>
       RESEARCH YEAR                    FUNDING                 FTE LEVEL
             <S>                         <C>                      <C>
             4                           [***]                    [***]
             5                           [***]                    [***]
             6                           [***]                    [***]
</Table>

     Research Year 1 will be deemed to have commenced on May 1, 2000. Payments
due for each Research Year shall be made quarterly in advance on or before
May 1, August 1, November 1 and February 1 of each Research Year except that the
quarterly payment due May 1, 2000 was made within thirty business days after the
Effective Date of this Research Agreement. All payments shall be made without
deduction for withholding or other similar taxes, in United States dollars to
the credit of such bank account as may be designated by VERTEX in writing to
NOVARTIS. Any payments which fall due on a date which is a legal holiday in the
Commonwealth of Massachusetts may be made on the next following day which is not
a legal holiday in the Commonwealth.

     3.3.          DEVELOPMENT LOAN FACILITY.
            The existing development loan facility is hereby terminated. All
currently outstanding loans made under the facility will be repaid by VERTEX on
or before the earlier of: May 7, 2008, as specified in Section 3.3.3 of the
Original Agreement; or the first anniversary of the effective date of any
termination of this Research Agreement by NOVARTIS for cause under Section 9.2
hereof. Notwithstanding the foregoing, the provisions of Section 4.8 of this
Research Agreement will apply as specified therein to repayment of development
loans advanced on account of the Compounds known as VX-680 and VX-528.

     3.4.          RECORDS.
            VERTEX shall keep accurate records and books of accounts containing
all data reasonably required for the calculation and verification of FTE's
employed by VERTEX in the Research Program.

            At NOVARTIS's request, VERTEX shall make those records available, no
more than once a year, during reasonable working hours, for review by a
recognized independent accounting firm acceptable to both parties, at NOVARTIS's
expense, for the sole purpose of verifying the accuracy of those records in the
calculation of Research Program FTE's. VERTEX shall not, however, be required to
retain or make available to NOVARTIS or its accountants, any such records or
books of account for any Research Year, beyond thirty-six (36) months from the
conclusion of that Research Year. NOVARTIS shall cause the accounting firm to
retain all such information in confidence.

            In the event of a negative difference between the average number of
FTE's stated to be involved in the Research Program and the number of FTE's
actually employed, the amount previously advanced to VERTEX and attributable to
any such negative difference shall be due and payable to NOVARTIS without delay.
If the negative difference is more than [***] in any Research Year, then VERTEX
shall also pay the reasonable costs of the independent accountant employed by
NOVARTIS in the review. Interest at the rate of [***], assessed from the end of

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 11
<Page>

the Research Year to which the negative difference relates, shall be due from
VERTEX upon prior written notice.

                                   ARTICLE IV
                LICENSE, DEVELOPMENT AND COMMERCIALIZATION RIGHTS

     4.1.          DEVELOPMENT ELECTION.
               (a) NOVARTIS shall have the exclusive right (the "Development
Election") to develop and commercialize, under the terms and conditions set
forth in the License Agreement and for any and all Indications, (i) each Drug
Product Candidate proposed to it by VERTEX as set forth below, and related
Back-up Compounds as provided in Section 4.5 hereof and selected by NOVARTIS,
and (ii) any Compound or Compounds selected by NOVARTIS, as provided in Section
4.1(d) hereof, from Compounds which have met the Development Candidate Criteria,
whether or not any such Compound or Compounds have been proposed as Development
Candidates by VERTEX. While the Development Election is in effect, VERTEX will
not grant to any Third Party rights to VERTEX Kinase Technology which are
inconsistent with the grant of the Development Election to NOVARTIS hereunder.
NOVARTIS's right to exercise Development Elections will expire and NOVARTIS
shall no longer have the right to select Drug Candidates hereunder upon the
first to occur of:

               (1) The Final Termination Date as defined below;

               (2) Termination of the Research Program by VERTEX under
                   Section 9.3 hereof;

               (3) Termination of the Research Program by either party
                   hereto for Scientific Cause under Section 9.5 hereof.

               If NOVARTIS validly terminates the Research Program for cause
               under Section 9.2 hereof, the Development Election may
               nonetheless be exercised for the one-year period after the
               effective date of the termination for cause, but only with
               respect to Compounds which have met the Development Candidate
               Criteria prior to the effective termination date.

               (b) VERTEX shall notify NOVARTIS and the JRC each time VERTEX has
identified a Compound that, in the reasonable exercise of its scientific and
business judgment, is a suitable Development Candidate and meets the Development
Candidate Criteria. The corresponding notice shall be accompanied by the
Development Candidate Information relating to the Development Candidate and its
Back-up Compounds, provided that information concerning Compound structures
shall be handled as specified in Section 5.1 hereof. NOVARTIS may, at its sole
discretion, exercise its Development Election and accept the Development
Candidate as a Drug Product Candidate by delivery of written notice to VERTEX
[***]. The total period of time from receipt of notice from VERTEX through [***]
shall be referred to as the "Notice Period". Notwithstanding any other
provisions of this Research Agreement, the Development Election with respect to
any Development Candidate will not expire until the end of the Notice Period
with respect to that Development Candidate.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 12
<Page>

               (c) [This subsection has been intentionally left blank.]

               (d) VERTEX will submit a final report (the "Final Report") to
NOVARTIS covering the period beginning on the Research Termination Date [***]
(the "Final Report Period"). The Final Report will contain Development Candidate
Information for any Compound that VERTEX believes, in the reasonable exercise of
its scientific and business judgment, meets the Development Candidate Criteria
[***], along with information with respect to relevant Back-up Compounds. The
procedure whereby NOVARTIS may exercise its Development Election and accept any
Development Candidate identified in the Final Report, for further development as
a Drug Product Candidate, will be the same as that described in subsection (b)
above, and the time period from receipt of the Final Report from VERTEX through
the end of the 90-day period referenced in that subsection (b) shall be called
the "Final Notice Period".

               In addition, [***] If NOVARTIS, based on this information,
               concludes that a given Compound does meet the Development
               Candidate Criteria, a formal Development Election procedure
               pursuant to Section 4.1(b) will be initiated for such Compound.
               If VERTEX disagrees with NOVARTIS's judgment that a given
               Compound meets the Development Candidate Criteria, the dispute
               resolution provisions in Section 2.5.2(ii) shall apply.

               The date upon which the Final Report Period, as and if extended
               by the parties as provided for in Section 4.3 hereof, expires
               shall be called the "Final Termination Date."

               (e) [***]

               (f) Promptly following exercise by NOVARTIS of its Development
Election, the parties will execute a License Agreement substantially identical
to the license agreement attached hereto as Exhibit A. NOVARTIS will develop and
commercialize the Drug Product Candidate under the provisions of the License
Agreement. If the Development Election has previously been exercised with
respect to another Drug Product Candidate and a License Agreement is in effect,
then the License Agreement will be amended to reflect the addition of another
Drug Product Candidate. Development of each Drug Product Candidate shall proceed
immediately after the Development Election is exercised, in accordance with the
terms of the License Agreement.

     4.2.          [This section has been intentionally left blank.]

     4.3.          EXTENSION OF NOTICE PERIOD AND FINAL NOTICE PERIOD.

            NOVARTIS may propose to VERTEX by written notice delivered during
[***] the Notice Period with respect to a particular Development Candidate, or
the Final Notice Period, with specific reference to one or more Compounds
included in the Final Report and meeting the Development Candidate Criteria,
that the Notice Period or the Final Notice Period, as the case may be, for a
specific Development Candidate or Compound be extended for good reason for a
specified time to permit NOVARTIS, at its expense and under its direction, to
conduct such additional studies of that Development Candidate or Compound as may
be specified in the notice. VERTEX shall discuss this request with NOVARTIS and
the parties shall attempt in

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 13
<Page>

good faith to reach mutual agreement with respect to the requested extension
period and the conduct of additional studies, but failing agreement the
applicable Notice Period or Final Notice Period shall expire as specified
herein.

     4.4.   REFUSED CANDIDATE.

            4.4.1. If NOVARTIS does not exercise its Development Election within
the Notice Period or the Final Notice Period, as applicable, specified in
Section 4.1, with respect to a particular Development Candidate proposed by
VERTEX, then the Development Election will expire with respect to that
Development Candidate (a "Refused Candidate"), and (a) NOVARTIS will relinquish
all rights under this Research Agreement and the License Agreement [***] (b)
VERTEX may thereafter develop and commercialize the Refused Candidate and any
such Excluded Compounds at its expense free of any further obligation to
NOVARTIS with respect thereto; and [***], shall be considered Excluded Compounds
under the provisions of this Section 4.4.1.

            4.4.2. [This section has been intentionally left blank.]

     4.5.          BACK-UP COMPOUNDS.
            The following provisions will apply with respect to Back-up
Compounds to any Drug Product Candidate.

               (a) VERTEX RESTRICTIONS ON NOMINATION AND DEVELOPMENT. So long as
NOVARTIS is using commercially reasonable efforts with respect to the
development of a particular Drug Product Candidate or the commercialization of a
particular Drug Product, VERTEX will not (i) propose a Compound for development
under the License Agreement which is a Back-up Compound with respect to that
Drug Product Candidate or Drug Product, or (ii) until after the period starting
on the date on which NOVARTIS has exercised its Development Election for a
particular Drug Product Candidate and ending [***] (the "Lead Period"), commence
development of that Back-up Compound either directly or together with or through
an Affiliate or a Third Party.

               (b) TERMINATION OF DEVELOPMENT OR COMMERCIALIZATION. If, prior to
the end of the Lead Period with respect to a particular Drug Product or Drug
Product Candidate, NOVARTIS ceases to use commercially reasonable efforts to
develop or commercialize that Drug Product Candidate or Drug Product, then the
restrictions on nomination and development referenced in subsection (a) above
will no longer apply with respect to Back-up Compounds for that Drug Product
Candidate or Drug Product unless NOVARTIS, without delay, commences another
Development Program under the License Agreement with another Compound (a
"Replacement Candidate") targeting the same Kinase, which Replacement Candidate
is a Back-up Compound associated with the discontinued Drug Product Candidate or
Drug Product, and NOVARTIS shall have the right to select for this purpose any
such Back-up Compound by providing VERTEX with notice of its Development
Election in this regard. Any such Back-up Compound for which NOVARTIS has
exercised its Development Election under this subsection (b) shall hereafter be
a Drug Product Candidate subject to the terms and conditions of the License
Agreement.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 14
<Page>

               (c) TERMINATION OF RIGHTS TO BACK-UP COMPOUNDS. A Back-up
Compound will no longer be subject to NOVARTIS's Development Election under the
Research Agreement after the end of the Lead Period applicable to that Back-up
Compound, except for Back-up Compounds which (i) subject to subsection (a)
above, VERTEX has proposed for development on or before the Final Termination
Date, and as to which NOVARTIS has exercised its Development Election hereunder;
or (ii) have been or will be selected by NOVARTIS for development before the end
of the applicable Lead Period under the provisions of subsection (b) above, or
(iii) for which NOVARTIS has exercised or will exercise its Development Election
before the end of the applicable Lead Period under the provisions of subsection
(d) below.

               (d) NOVARTIS RIGHTS TO LICENSE BACK-UP COMPOUNDS. Anytime prior
to the expiry of the Lead Period with respect a particular Drug Product
Candidate, NOVARTIS may also, by paying in each case the Back-up Election Fee
provided under Section 6.1 of the License Agreement, exercise its Development
Election with respect to any one or more Back-up Compounds associated with that
Drug Product Candidate, provided that Drug Product Candidate, or a Back-up
Compound selected pursuant to the provisions of subsection (b) above, is still
in active development. Any such Back-up Compound for which NOVARTIS has
exercised its Development Election under this subsection (d) shall become a
"Drug Product Candidate Back-up Candidate" subject to the terms and conditions
of the License Agreement.

               (e) NOVARTIS OBLIGATIONS WITH RESPECT TO DRUG PRODUCT CANDIDATE
BACK-UP CANDIDATES. So long as NOVARTIS is using commercially reasonable
efforts, pursuant to the provisions of Sections 3.6 and 5.6 of the License
Agreement, with respect to the development of a particular Drug Product
Candidate or the commercialization of a particular Drug Product, NOVARTIS shall
have no obligation to develop any of the Drug Product Candidate Back-up
Candidates associated with that Drug Product Candidate or Drug Product. As soon
as NOVARTIS ceases the development of a particular Drug Product Candidate,
NOVARTIS's obligations to use diligent, commercially reasonable efforts will
immediately shift from the discontinued Drug Product Candidate to an associated
Drug Product Candidate Back-up Compound. If NOVARTIS ceases the development of a
particular Drug Product Candidate and does not commence development of a Drug
Product Candidate Back-up Compound pursuant to the foregoing, the license to the
Drug Product Candidate and its Back-up Compounds under the License Agreement
will expire and the license rights will revert to VERTEX.

     4.6.   [This section has been intentionally left blank.]

     4.7.   DRUG SUBSTANCE.

            As soon as practicable after the exercise of its Development
Election with respect to a Drug Product Candidate, VERTEX will deliver to
NOVARTIS, if so requested by NOVARTIS, all drug substance for that Candidate in
VERTEX's possession, if any, to the extent it is usable in connection with
development of that Candidate. NOVARTIS will reimburse VERTEX for the
Manufacturing Cost (as such term is defined in the License Agreement) of that
material within thirty (30) days of receipt of VERTEX's invoice therefor.

     4.8.   SPECIAL PROVISIONS REGARDING VX-680, VX-528 AND VX-608.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 15
<Page>

            The parties acknowledge that VERTEX is currently pursuing three
Development Candidates which have been designated as VX-608, VX-680 and VX-528.

               (a) VX-608. VX-608 will be governed by this Research Agreement
and will be subject to the Development Election. The Notice Period with respect
to VX-608 shall be deemed to have commenced on the later of (i) the date on
which this Research Agreement is entered into, or (ii) the date by which
NOVARTIS is in possession of the Development Candidate Information. If NOVARTIS
exercises its Development Election with respect to VX-608 during the Notice
Period, that Compound will become a Drug Product Candidate hereunder, and
NOVARTIS will undertake all future development of VX-608 under the terms of the
License Agreement. The Development Election Payment will be made to VERTEX and
[***]. If NOVARTIS fails to exercise its Development Election with respect to
VX-608 during the Notice Period, then VX-608 will become a Refused Candidate
hereunder and the provisions of Section 4.4 will be applicable thereafter. Any
outstanding development loan will be repaid in accordance with Section 3.3
hereof.

               (b) VX-680 AND VX-528. The Compounds designated by VERTEX as
VX-680 and VX-528 are in early development under the provisions of the Original
Agreement, and the terms of the Original Agreement shall continue to govern the
rights and obligations of VERTEX and NOVARTIS with respect to VX-680 and VX-528
only, with the following modifications: [***]

               At its sole discretion exercisable by notice in writing from
               VERTEX to NOVARTIS delivered on or before [***], VERTEX may elect
               to consider VX-680 and VX-528 as Development Candidates which
               have become Refused Candidates under the Research Agreement, and
               the terms and conditions of the Research Agreement as they apply
               to any Refused Candidate shall thereafter apply in the case of
               VX-680 and VX-528. Contemporaneously with the aforementioned
               notice, VERTEX shall repay to NOVARTIS that portion of the total
               amount of any development loan previously advanced by NOVARTIS to
               VERTEX on account of either Compound, which is unspent and
               uncommitted as of the notice date. The balance of any development
               loan shall be repaid as provided in Section 3.3 hereof.

                                    ARTICLE V
                                 CONFIDENTIALITY

     5.1.   UNDERTAKING.
            During the term of this Research Agreement, each party shall keep
confidential, and other than as provided herein shall not use or disclose,
directly or indirectly, any trade secrets, confidential or proprietary
information, or any other knowledge, information, documents or materials, owned,
developed or possessed by the other party, whether in tangible or intangible
form, the confidentiality of which such other party takes reasonable measures to
protect, including but not limited to VERTEX Kinase Technology and NOVARTIS
Kinase Technology.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 16
<Page>

                (a) Each party shall take any and all lawful measures to prevent
the unauthorized use and disclosure of such information, and to prevent
unauthorized persons or entities from obtaining or using such information.

                (b) Each party further agrees to refrain from directly or
indirectly taking any action which would constitute or facilitate the
unauthorized use or disclosure of such information. Each party may disclose such
information to its officers, employees and agents, to authorized licensees and
sublicensees, and to subcontractors in connection with the development or
manufacture of Drug Candidates, Drug Product Candidates or Drug Products, to the
extent necessary to enable such parties to perform their obligations hereunder
or under the applicable license, sublicense or subcontract, as the case may be;
provided, that such officers, employees, agents, licensees, sublicensees and
subcontractors have entered into appropriate confidentiality agreements for
secrecy and non-use of such information which by their terms shall be
enforceable by injunctive relief at the instance of the disclosing party.

                (c) Each party shall be liable for any unauthorized use and
disclosure of such information by its officers, employees and agents and any
such sublicensees and subcontractors.

            (d) NOVARTIS will ensure that information with respect to the
                chemical structure of any Development Candidate which is
                delivered to NOVARTIS under Section 4.1(b) hereof as part of the
                Development Candidate Information with respect to that
                Development Candidate and its associated Back-up Compounds will
                be distributed or otherwise made known only to [***] The
                foregoing limitation on distribution of information will cease
                being applicable at such time as NOVARTIS exercises its
                Development Election with respect to that Development Candidate.

     5.2.   EXCEPTIONS.
            Notwithstanding the foregoing, the provisions of Section 5.1 hereof
shall not apply to knowledge, information, documents or materials which the
receiving party can conclusively establish:

                (a) have entered the public domain without such party's breach
of any obligation owed to the disclosing party;

                (b) are permitted to be disclosed by the prior written consent
of the disclosing party;

                (c) have become known to the receiving party from a source other
than the disclosing party, other than by breach of an obligation of
confidentiality owed to the disclosing party;

                (d) are disclosed by the disclosing party to a Third Party
without restrictions on its disclosure;

                (e) are independently developed by the receiving party without
breach of this Research Agreement; or

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 17
<Page>

                (f) are required to be disclosed by the receiving party to
comply with applicable laws or regulations, to defend or prosecute litigation or
to comply with governmental regulations, provided that the receiving party
provides prior written notice of such disclosure to the disclosing party and
takes reasonable and lawful actions to avoid or minimize the degree of such
disclosure.

            Either VERTEX or NOVARTIS may at any time, by notice in writing to
the other party, waive any or all of the confidentiality obligations to which
the other party is subject hereunder, for any length of time or with respect to
any specific information.

     5.3.   PUBLICITY.
            The parties will agree upon the timing and content of any initial
press release or other public communications relating to this First Revised and
Restated Agreement and the transactions contemplated herein.

                (a) Except to the extent already disclosed in that initial press
release or other public communication, no public announcement concerning the
existence or the terms of this Research Agreement or concerning the transactions
described herein shall be made, either directly or indirectly, by VERTEX or
NOVARTIS, except as may be legally required by applicable laws, regulations, or
judicial order, without first obtaining the approval of the other party and
agreement upon the nature, text, and timing of such announcement, which approval
and agreement shall not be unreasonably withheld.

                (b) The party desiring to make any such public announcement
shall provide the other party with a written copy of the proposed announcement
in sufficient time prior to public release to allow such other party to comment
upon such announcement, prior to public release.

     5.4.   SURVIVAL.
            The provisions of this Article V shall survive the termination of
this Research Agreement and shall extend for a period of five (5) years
thereafter.

                                   ARTICLE VI
                                   PUBLICATION

     Each of NOVARTIS and VERTEX reserves the right to publish or publicly
present the results (the "Results") of the Research Program, subject to the
following terms and conditions. The party proposing to publish or publicly
present the Results (the "publishing party") will submit a draft of any proposed
manuscript or speech to the other party (the "non-publishing party") for
comments at least thirty (30) days prior to submission for publication or oral
presentation. The non-publishing party shall notify the publishing party in
writing within fifteen (15) days of receipt of such draft whether such draft
contains (i) information of the non-publishing party which it considers to be
confidential under the provisions of Article V hereof, (ii) information that if
published would have an adverse effect on a patent application covering the
subject matter of this Research Agreement which the non-publishing party intends
to file, or (iii) information which the non-publishing party reasonably believes
would be likely to have a material adverse impact on the development or
commercialization of a Drug Product Candidate. In any such notification, the
non-publishing party shall indicate with specificity its suggestions

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 18
<Page>

regarding the manner and degree to which the publishing party may disclose such
information. In the case of item (ii) above, the non-publishing party may
request a delay and the publishing party shall delay such publication, for a
period not exceeding ninety (90) days, to permit the timely preparation and
filing of a patent application or an application for a certificate of invention
on the information involved. In the case of item (i) above, no party may publish
confidential information of the other party without its consent in violation of
Article V of this Research Agreement. In the case of item (iii) above, if the
publishing party shall disagree with the non-publishing party's assessment of
the impact of the publication, then the issue shall be referred to the JSC for
resolution. If the JSC is unable to reach agreement on the matter within thirty
(30) days after such referral, the matter shall be referred by the JSC to the
Chief Executive Officer of NOVARTIS and the Chief Executive Officer of VERTEX
who shall attempt in good faith to reach a fair and equitable resolution of this
disagreement. If the disagreement is not resolved in this manner within two (2)
weeks of referral by the JSC as aforesaid, then the decision of the publishing
party as to publication of any information generated by it, subject always to
the confidentiality provisions of Article V hereof, shall be final, provided
that such decision shall be exercised with reasonable regard for the interests
of the non-publishing party. The parties agree that authorship of any
publication will be determined based on the customary standards then being
applied in the relevant scientific journal. The parties will use their best
efforts to gain the right to review proposed publications relating to the
subject matter of the Research Program by consultants or contractors.

     This Article VI shall terminate with the termination of this Research
Agreement, but the provisions of Article V hereof shall continue to govern the
disclosure by one party, whether by publication or otherwise, of Confidential
Information of the other, during the period set forth in Section 5.4.

                                   ARTICLE VII
                                 INDEMNIFICATION

     7.1.   INDEMNIFICATION BY VERTEX.
            VERTEX will indemnify and hold NOVARTIS and its Affiliates, and
their employees, officers and directors harmless against any loss, damages,
action, suit, claim, demand, liability, expense, bodily injury, death or
property damage (a "Loss"), that may be brought, instituted or arise against or
be incurred by such persons to the extent such Loss is based on or arises out
of:

                (a) the development, manufacture, use, sale, storage or handling
of a Compound, a Development Candidate, a Drug Product Candidate or a Drug
Product by VERTEX or its Affiliates or their representatives, agents, authorized
sublicensees or subcontractors under this Research Agreement, or any actual or
alleged violation of law resulting therefrom (with the exception of Losses based
on infringement or misappropriation of intellectual property rights); or

                (b) the breach by VERTEX of any of its covenants,
representations or warranties set forth in this Research Agreement; and

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 19
<Page>

                (c) provided however, that the foregoing indemnification shall
not apply to any Loss to the extent such Loss is caused by the negligent or
willful misconduct of NOVARTIS or its Affiliates.

     7.2.   INDEMNIFICATION BY NOVARTIS.
            NOVARTIS will indemnify and hold VERTEX, and its Affiliates, and
their employees, officers and directors harmless against any Loss that may be
brought, instituted or arise against or be incurred by such persons to the
extent such Loss is based on or arises out of:

                (a) the development, manufacture, use, sale, storage or handling
of a Compound, a Development Candidate, a Drug Product Candidate or a Drug
Product by NOVARTIS or its Affiliates or their representatives, agents,
authorized sublicensees or subcontractors under this Research Agreement, or any
actual or alleged violation of law resulting therefrom (with the exception of
Losses based on infringement or misappropriation of intellectual property
rights); or

                (b) the breach by NOVARTIS of any of its covenants,
representations or warranties set forth in this Research Agreement; and

                (c) provided that the foregoing indemnification shall not apply
to any Loss to the extent such Loss is caused by the negligent or willful
misconduct of VERTEX or its Affiliates.

     7.3.   CLAIMS PROCEDURES.
            Each Party entitled to be indemnified by the other Party (an
"Indemnified Party") pursuant to Section 7.1 or 7.2 hereof shall give notice to
the other Party (an "Indemnifying Party") promptly after such Indemnified Party
has actual knowledge of any threatened or asserted claim as to which indemnity
may be sought, and shall permit the Indemnifying Party to assume the defense of
any such claim or any litigation resulting therefrom; provided:

                (a) That counsel for the Indemnifying Party, who shall conduct
the defense of such claim or any litigation resulting therefrom, shall be
approved by the Indemnified Party (whose approval shall not unreasonably be
withheld) and the Indemnified Party may participate in such defense at such
party's expense (unless (i) the employment of counsel by such Indemnified Party
has been authorized by the Indemnifying Party; or (ii) the Indemnified Party
shall have reasonably concluded that there may be a conflict of interest between
the Indemnifying Party and the Indemnified Party in the defense of such action,
in each of which cases the Indemnifying Party shall pay the reasonable fees and
expenses of one law firm serving as counsel for the Indemnified Party, which law
firm shall be subject to approval, not to be unreasonably withheld, by the
Indemnifying Party); and

                (b) The failure of any Indemnified Party to give notice as
provided herein shall not relieve the Indemnifying Party of its obligations
under this Research Agreement to the extent that the failure to give notice did
not result in harm to the Indemnifying Party.

                (c) No Indemnifying Party, in the defense of any such claim or
litigation, shall, except with the approval of each Indemnified Party which
approval shall not be unreasonably withheld, consent to entry of any judgment or
enter into any settlement which (i)

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 20
<Page>

would result in injunctive or other relief being imposed against the Indemnified
Party; or (ii) does not include as an unconditional term thereof the giving by
the claimant or plaintiff to such Indemnified Party of a release from all
liability in respect to such claim or litigation.

                (d) Each Indemnified Party shall furnish such information
regarding itself or the claim in question as an Indemnifying Party may
reasonably request in writing and shall be reasonably required in connection
with the defense of such claim and litigation resulting therefrom.

     7.4.   COMPLIANCE.
            The parties shall comply fully with all applicable laws and
regulations in connection with their respective activities under this Research
Agreement.

                                  ARTICLE VIII
                              PATENTABLE INVENTIONS

     8.1.   OWNERSHIP.
            All inventions made and all Know-How generated exclusively by either
party or its Affiliates (directly or through others acting on its behalf) prior
to and during the term of this Research Agreement shall be owned by the party
making the invention or generating the Know-How claimed, or if such invention is
made jointly (a "Joint Invention"), shall be owned jointly, all as determined in
accordance with United States laws of inventorship.

     8.2.   PREPARATION.
            VERTEX shall take responsibility for the preparation, filing,
prosecution and maintenance of all VERTEX Patents, and any patents and patent
applications claiming Joint Inventions, and NOVARTIS shall take responsibility
for the preparation, filing, prosecution and maintenance of all NOVARTIS
Patents. VERTEX shall provide the JRC with periodic reports listing, by name,
Patents filed by VERTEX in the United States and other jurisdictions, along with
a general summary of the claims made and the jurisdictions of filing. In good
time, before the deadline for foreign filing of any patent application filed in
the United States, VERTEX will notify NOVARTIS whether it intends to foreign
file such patent application, and if it intends to do so, in what countries it
proposes to foreign file. Upon timely written notice from NOVARTIS, VERTEX will
file in such additional countries -- all being countries in which NOVARTIS would
customarily file its own cases dealing with similar subject matter -- as
NOVARTIS shall request.

     8.3.   COSTS.
            (a) During the Research Program. NOVARTIS shall reimburse VERTEX for
[***]. If the full amount of any reimbursement commitment is not applied in any
Research Year, the unused balance may be carried over from year to year during
the Research Program.

            (b) After the Research Program. Upon expiration of the Research
Program, the parties shall determine which Patents covering Drug Product
Candidates and Drug Products, and Development Candidates and Back-up Compounds
as to which the Development Election is still applicable (until it expires), are
included in the Kinase Technology, and thereafter [***]. Either party may at any
time thereafter elect, by written notice to the other party, to discontinue
support for one or more such Patents (a "Discontinued Patent") and shall not be
responsible for any costs

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 21
<Page>

relating to a Discontinued Patent which are incurred more than sixty (60) days
after receipt of that notice by the other party. In such case, the other party
may elect at its sole discretion to continue preparation, filing, prosecution or
maintenance of the Discontinued Patent at its sole expense. The party so
continuing shall own any such Patent, and if the party electing to discontinue
support is the owner of the Discontinued Patent, it shall execute such documents
of transfer or assignment and perform such acts as may be reasonably necessary
to transfer ownership of the Discontinued Patent to the other party and enable
that party to file or to continue prosecution or maintenance, if the other party
elects to do so. Discontinuance may be on a country-by-country basis or for a
Patent series in total.

                                   ARTICLE IX
                              TERM AND TERMINATION

     9.1.   TERM.
            9.1.1. This Research Agreement shall have retroactive effect
to the Effective Date, replacing and superceding the rights and obligations of
the parties under the Original Agreement, except that the terms of the Original
Agreement shall be deemed to govern the rights and obligations of the parties
with respect to the Compounds known as VX-680 and VX-528, pursuant to the
provisions of Section 4.8 of this Research Agreement. This Research Agreement
will extend until the Final Termination Date as defined herein, unless earlier
terminated by either party hereto in accordance with this Research Agreement, or
unless extended by mutual agreement of the parties; provided that the Agreement
will be deemed to continue in effect with respect to any Drug Product Candidate
during the Lead Period with respect to that Candidate, but only insofar as
necessary to enable NOVARTIS to exercise its Development Election under Section
4.5 hereof with respect to any Back-up Compounds for that Drug Product
Candidate.

     9.2.   TERMINATION OF THE RESEARCH PROGRAM BY NOVARTIS FOR CAUSE.
            Upon written notice to VERTEX, NOVARTIS may at its sole discretion
unilaterally terminate the Research Program and this Research Agreement upon the
occurrence of any of the following events:

                (a) VERTEX shall materially breach any of its material
obligations, such as its obligations under Section 3.2 hereof, under this
Research Agreement or the License Agreement, and such material breach shall not
have been remedied or steps initiated to remedy the same to NOVARTIS's
reasonable satisfaction, within sixty (60) days after NOVARTIS sends written
notice of breach to VERTEX; or

                (b) VERTEX shall cease to function as a going concern by
suspending or discontinuing its business for any reason except for interruptions
caused by Force Majeure, strike, labor dispute or any other events over which it
has no control.

            In the event of any valid termination under this Section 9.2,
NOVARTIS shall not be required to make any payments under Section 3.2 hereof
which are not due and payable prior to receipt by VERTEX of the notice of breach
referenced under Section 9.2(a) or receipt by VERTEX of the notice of
termination pursuant to Section 9.2(b), as the case may be. Notwithstanding the
foregoing, any License Agreement then in effect shall continue in effect unless
it is expressly terminated in accordance with its terms.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 22
<Page>

     9.3.   TERMINATION OF THE RESEARCH PROGRAM BY VERTEX FOR CAUSE.
            VERTEX may at its sole discretion terminate this Research Agreement
upon written notice to NOVARTIS upon the occurrence of any of the following
events:

                (a) NOVARTIS shall materially breach any of its material
obligations under this Research Agreement or the License Agreement and such
material breach shall not have been remedied or steps initiated to remedy the
same to VERTEX's reasonable satisfaction, within sixty (60) days after VERTEX
sends written notice of breach to NOVARTIS; or

                (b) NOVARTIS shall cease to function as a going concern by
suspending or discontinuing its business for any reason except for interruptions
caused by Force Majeure, strike, labor dispute or any other events over which it
has no control.

            Notwithstanding the foregoing, any License Agreement then in effect
shall continue in effect unless it is expressly terminated in accordance with
its terms.

     9.4.   [This section has been intentionally left blank.]

     9.5.   TERMINATION FOR SCIENTIFIC CAUSE.

            Either party may terminate this Research Agreement upon six months'
prior written notice to the other party, if the terminating party can
demonstrate to the reasonable satisfaction of the other party that, by reason of
scientific developments unknown on the Effective Date, the Research Program is
unlikely to produce any Compounds that can achieve a commercially viable
therapeutic effect through an effect on a Kinase target.

     9.6.   EFFECT OF TERMINATION.
                (a) Except where explicitly provided elsewhere herein,
termination of this Research Agreement for any reason, or expiration of this
Research Agreement, will not affect: (i) obligations which have accrued as of
the date of termination or expiration, and (ii) obligations and rights which,
expressly or from the context thereof, are intended to survive termination or
expiration of this Research Agreement, including obligations of confidentiality
under Article V hereof, the indemnification provisions of Article VII hereof and
the rights and obligations of the parties during the Lead Period under Sections
4.1 and 4.5 with respect to a particular Drug Product Candidate and related
Back-up Compounds.

                (b) Upon termination or expiration of this Research Agreement,
NOVARTIS and VERTEX will retain exclusive rights to their respective Kinase
Technology (including intellectual property), except NOVARTIS shall hold those
rights to VERTEX Technology provided in any License Agreement in effect on the
Final Termination Date covering Drug Product Candidates selected by NOVARTIS,
and shall hold those rights to Back-up Compounds and Drug Product Candidate
Back-up Compounds provided in Sections 4.1(e) and 4.5.

                                    ARTICLE X
                         REPRESENTATIONS AND WARRANTIES

    10.1.   REPRESENTATIONS AND WARRANTIES OF VERTEX.
            VERTEX represents and warrants to NOVARTIS as follows:

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 23
<Page>

                (a) Authorization. This Research Agreement has been duly
executed and delivered by VERTEX and constitutes the valid and binding
obligation of VERTEX, enforceable against VERTEX in accordance with its terms
except as enforceability may be limited by bankruptcy, fraudulent conveyance,
insolvency, bankruptcy, reorganization, moratorium and other laws relating to or
affecting creditors' rights generally and by general equitable principles. The
execution, delivery and performance of this Research Agreement have been duly
authorized by all necessary action on the part of VERTEX, its officers and
directors.

                (b) No Third Party Rights. VERTEX owns or possesses adequate
licenses or other rights to use all VERTEX Kinase Technology relating to the
Field and to grant the licenses herein. The granting of the Development Election
to NOVARTIS hereunder does not violate any right known to VERTEX of any Third
Party.

                (c) Third Party Patents. Except as disclosed in writing between
the parties to this Research Agreement or their respective agents, VERTEX is not
aware of any issued patents or pending patent applications that, if issued,
would be infringed by the development, manufacture, use or sale of any Compound,
Development Candidate or Drug Product Candidate pursuant to this Research
Agreement.

    10.2.   REPRESENTATIONS AND WARRANTIES OF NOVARTIS.
            NOVARTIS represents and warrants to VERTEX as follows:
                (a) Authorization. This Research Agreement has been duly
executed and delivered by NOVARTIS and constitutes the valid and binding
obligation of NOVARTIS, enforceable against NOVARTIS in accordance with its
terms except as enforceability may be limited by bankruptcy, fraudulent
conveyance, insolvency, bankruptcy, reorganization, moratorium and other laws
relating to or affecting creditors' rights generally and by general equitable
principles. The execution, delivery and performance of this Research Agreement
have been duly authorized by all necessary action on the part of NOVARTIS, its
officers and directors.

                (b) Third Party Rights. NOVARTIS owns or possesses adequate
licenses or other rights to use all NOVARTIS Kinase Technology relating to the
Field in accordance with the provisions of this Research Agreement.

                (c) Third Party Patents. Except as disclosed in writing between
the parties to this Research Agreement or their respective agents, NOVARTIS is
not aware of any issued patents or pending patent applications that, if issued,
would be infringed by the development, manufacture, use or sale of any Compound,
Development Candidate or Drug Product Candidate pursuant to this Research
Agreement.

                                   ARTICLE XI
                               DISPUTE RESOLUTION

    11.1.   GOVERNING LAW, AND JURISDICTION.
            This Research Agreement shall be governed and construed in
accordance with the internal laws of the State of New York.

    11.2.   DISPUTE RESOLUTION PROCESS.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 24
<Page>

                (a) General. Except as set forth in (b) below or as otherwise
explicitly provided herein, in the event of any controversy or claim arising out
of or relating to any provision of this Research Agreement, or the collaborative
effort contemplated hereby, the parties shall, and either party may, initially
refer such dispute to the JSC, and failing resolution of the controversy or
claim within thirty (30) days after such referral, the matter shall be referred
to the Chief Executive Officer of VERTEX and the Chief Executive Officer of
NOVARTIS who shall, as soon as practicable, attempt in good faith to resolve the
controversy or claim. If such controversy or claim is not resolved within sixty
(60) days of the date of initial referral of the matter to the JSC, either party
shall be free to initiate proceedings in any court having requisite
jurisdiction.

                (b) Third Party Referral. Any dispute or claim relating to the
"Referral Matters" as defined below which the parties are unable to resolve
pursuant to the other dispute resolution mechanisms provided in this Research
Agreement (other than litigation) shall, upon the written request of one party
delivered to the other party, be submitted to and settled by a panel of Third
Parties (a "Third Party Panel") appointed by VERTEX and NOVARTIS as provided
below. The "Referral Matter" shall consist solely of disagreements concerning
whether a particular Compound has satisfied all of the applicable Development
Candidate Criteria. Within thirty (30) days after delivery of the
above-referenced written request, each party will appoint one person who is not
an Affiliate of the party appointing that person, and who is knowledgeable in
the areas of pharmaceutical science, business and commercial aspects of drug
development and sale, or the clinical development of pharmaceuticals, to hear
and determine the dispute. The two persons so chosen will select another
impartial Third Party and their majority decision will be final and conclusive
upon the parties hereto. If either party fails to designate its appointee within
the thirty (30) day period referenced above, then the appointee who has been
designated by the other party will serve as the sole member of the Third Party
Panel and will be deemed to be the single, mutually approved party to resolve
the dispute. Each party will bear its own costs in the Third Party Referral
process, and the parties will split equally the costs of the Third Party Panel
members. The Third Party Panel will, upon the request of either party, issue its
final determination in writing.

                                   ARTICLE XII
                            MISCELLANEOUS PROVISIONS

    12.1.   OFFICIAL LANGUAGE.
            English shall be the official language of this Research Agreement
and the License Agreement, and all communications between the parties hereto
shall be conducted in that language.

    12.2.   WAIVER.
            No provision of this Research Agreement may be waived except in
writing by both parties hereto. No failure or delay by either party hereto in
exercising any right or remedy hereunder or under applicable law will operate as
a waiver thereof, or a waiver of any right or remedy on any subsequent occasion.

    12.3.   FORCE MAJEURE.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 25
<Page>

            Neither party will be in breach hereof by reason of its delay in the
performance of or failure to perform any of its obligations hereunder, if that
delay or failure is caused by strikes, acts of God or the public enemy, riots,
incendiaries, interference by civil or military authorities, compliance with
governmental priorities for materials, or any fault beyond its control or
without its fault or negligence.

    12.4.   SEVERABILITY.
            Should one or more provisions of this Research Agreement be or
become invalid, then the parties hereto shall attempt to agree upon valid
provisions in substitution for the invalid provisions, which in their economic
effect come so close to the invalid provisions that it can be reasonably assumed
that the parties would have accepted this Research Agreement with those new
provisions. If the parties are unable to agree on such valid provisions, the
invalidity of such one or more provisions of this Research Agreement shall
nevertheless not affect the validity of the Agreement as a whole, unless the
invalid provisions are of such essential importance for this Research Agreement
that it may be reasonably presumed that the parties would not have entered into
this Research Agreement without the invalid provisions.

    12.5.   GOVERNMENT ACTS.
            In the event that any act, regulation, directive, or law of a
country or its government, including its departments, agencies or courts, should
make impossible or prohibit, restrain, modify or limit any material act or
obligation of NOVARTIS or VERTEX under this Research Agreement, the party, if
any, not so affected, shall have the right, at its option, to suspend or
terminate this Research Agreement as to such country, if good faith negotiations
between the parties to make such modifications therein as may be necessary to
fairly address the impact thereof, are not successful after a reasonable period
of time in producing mutually acceptable modifications to this Research
Agreement.

    12.6.   GOVERNMENT APPROVALS.
            Each party will obtain any government approval required in its
country of domicile to enable this Research Agreement to become effective, or to
enable any payment hereunder to be made, or any other obligation hereunder to be
observed or performed. Each party will keep the other informed of progress in
obtaining any such government approval, and will cooperate with the other party
in any such efforts.

    12.7.   EXPORT CONTROLS.
            This Research Agreement is made subject to any restrictions
concerning the export of materials and Technology from the United States which
may be imposed upon or related to either party to this Research Agreement from
time to time by the Government of the United States. Furthermore, NOVARTIS will
not export, directly or indirectly, any VERTEX Kinase Technology or any Bulk
Drug Substance, Drug Product Candidates or Drug Products utilizing such
Technology to any countries for which the United States Government or any agency
thereof at the time of export requires an export license or other governmental
approval, without first obtaining the written consent to do so from the
Department of Commerce or other agency of the United States Government when
required by applicable statute or regulation.

    12.8.   ASSIGNMENT.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 26
<Page>

            This Research Agreement may not be assigned or otherwise transferred
by either party without the prior written consent of the other party; provided,
however, that either party may assign this Research Agreement, without the
consent of the other party, (i) to any of its Affiliates, if the assigning party
guarantees the full performance of its Affiliates' obligations hereunder, or
(ii) in connection with the transfer or sale of all or substantially all of its
assets or business or in the event of its merger or consolidation with another
company. Any purported assignment in contravention of this Section 12.8 shall,
at the option of the non-assigning party, be null and void and of no effect. No
assignment shall release either party from responsibility for the performance of
any accrued obligation of such party hereunder. This Research Agreement shall be
binding upon and enforceable against the successor to or any permitted assignees
from either of the parties hereto.

    12.9.   AFFILIATES.
            Each party may perform its obligations hereunder personally or
through one or more Affiliates, although each party shall nonetheless be solely
responsible for the performance of its Affiliates. Neither party shall permit
any of its Affiliates to commit any act (including any act or omission) which
such party is prohibited hereunder from committing directly. The use of
subcontractors by either party shall not increase the financial obligations of
the other party hereunder in any respect.

   12.10.   COUNTERPARTS.
            This Research Agreement may be executed in duplicate, each of which
shall be deemed to be original and both of which shall constitute one and the
same Agreement.

   12.11.   NO AGENCY.
            Nothing herein contained shall be deemed to create an agency, joint
venture, amalgamation, partnership or similar relationship between NOVARTIS and
VERTEX. Notwithstanding any of the provisions of this Research Agreement,
neither party to this Research Agreement shall at any time enter into, incur, or
hold itself out to third parties as having authority to enter into or incur, on
behalf of the other party, any commitment, expense, or liability whatsoever, and
all contracts, expenses and liabilities in connection with or relating to the
obligations of each party under this Research Agreement shall be made, paid, and
undertaken exclusively by such party on its own behalf and not as an agent or
representative of the other.

   12.12.   NOTICE.
            All communications between the parties with respect to any of the
provisions of this Research Agreement will be sent to the addresses set out
below, or to such other addresses as may be designated by one party to the other
by notice pursuant hereto, by prepaid, certified air mail (which shall be deemed
received by the other party on the seventh business day following deposit in the
mails), or by facsimile transmission, or other electronic means of communication
(which shall be deemed received when transmitted), with confirmation by first
class letter, postage pre-paid, given by the close of business on or before the
next following business day:

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 27
<Page>

            if to NOVARTIS, at:

                NOVARTIS PHARMA AG
                Business Development and Licensing
                P.O. Box
                CH-4002
                Basel, Switzerland
                Attention: Victor A. Hartmann, Vice President

            with a copy to: Legal Services, at the address referenced above

            if to VERTEX, at:
                Vertex Pharmaceuticals Incorporated
                130 Waverly Street
                Cambridge, MA U.S.A. 02139-4211
                Attention:  President

                 with a copy to: Legal Department
                Attention:  General Counsel

   12.13.   HEADINGS.
            The paragraph headings are for convenience only and will not be
deemed to affect in any way the language of the provisions to which they refer.

   12.14.   AUTHORITY.
            The undersigned represent that they are authorized to sign this
Research Agreement on behalf of the parties hereto. The parties each represent
that no provision of this Research Agreement will violate any other agreement
that such party may have with any other person or company. Each party has relied
on that representation in entering into this Research Agreement.

   12.15.   ENTIRE AGREEMENT.
            This Research Agreement, together with the Original Agreement
insofar as it remains applicable, as set forth in the Recitals, in Section 4.8
and elsewhere herein, with respect to VX-680 and VX-528 only, and the respective
License Agreements thereto, contains the entire understanding of the parties
relating to the matters referred to herein, and may only be amended by a written
document, duly executed on behalf of the respective parties.

   12.16.   STANDSTILL.
            [***]

   12.17.   NOTICE OF PHARMACEUTICAL SIDE-EFFECTS.
            During the term of this Research Agreement, the parties shall keep
each other promptly and fully informed and will promptly notify appropriate
authorities in accordance with applicable law, after receipt of information with
respect to any serious adverse event (as defined by the ICH Harmonized
Tripartite Guideline on Clinical Safety Data Management), directly or indirectly
attributable to the use or application of Compounds, a Development Candidate,
Bulk Drug Substance, a Drug Product Candidate or a Drug Product.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 28
<Page>

   12.18.   INFLATION ADJUSTMENT.
            All payments required to be made to VERTEX hereunder (except any
royalty payments required to be made under the provisions of Section 6.3 of the
License Agreement) shall be adjusted at the beginning of each Research Year
(commencing at the beginning of Research Year 2) to reflect the impact of
inflation since the Effective Date of the Agreement, as measured by the biotech
worker inflation rate defined and reported in the Radford Survey (Radford/AON
Consulting Inc., San Francisco, CA), or other mutually acceptable index.
Notwithstanding the foregoing, no adjustment shall be required in any Research
Year in which the appropriate inflation adjustment, if applied, would result in
a change of less than [***] in the relevant payment amount.

   12.19.   INVOICE REQUIREMENT.
            Any amounts payable to VERTEX hereunder (except any royalty payments
required to be made under the provisions of Section 6.3 of the License
Agreement) shall be made within thirty days after receipt by NOVARTIS, or its
nominee designated for that purpose in advance by NOVARTIS in writing to VERTEX,
of an invoice covering such payment, which invoice shall conform to the extent
reasonably practicable to the form of invoice contained in Exhibit B to this
Research Agreement.

   12.20.   HARDSHIP.
            If as a result of unforeseen events or developments relating to the
subject matter of this Research Agreement, the performance of this Research
Agreement shall cause inequitable economic hardship for one party which runs
counter to the objectives of this Research Agreement and which the other party
cannot reasonably and in good faith expect the first party to bear unrelieved,
the parties will meet and seek in good faith to find equitable means of amending
this Research Agreement to reestablish a fair and reasonable economic balance
under this Research Agreement between the parties hereto.

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 29
<Page>

                               VERTEX PHARMACEUTICALS INCORPORATED


                               By: /s/ Kenneth S. Boger
                                  ---------------------------------------------
                                      Kenneth S. Boger
                               Title: Senior Vice President and General Counsel


                               NOVARTIS PHARMA AG


                               By: /s/ Stephanie Lassarat
                                  ----------------------------------------------
                               Title: Senior Legal Counsel
                                     -------------------------------------------


                               By: /s/ W. Steiger
                                  ----------------------------------------------
                               Title: Head of Administration, NIBR Basil
                                     -------------------------------------------

                           First Revised and Restated
       Research and Early Development Agreement -- Confidential -- Page 30
<Page>

                                  SCHEDULE 1.13

                     EXCLUDED COMPOUNDS AND EXCLUDED KINASES

        Excluded Kinases

                                          SWISSPROT Designation

        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]
        [***]                                     [***]

        Excluded Compounds

        [***]


                           First Revised and Restated
             Research and Early Develoment Agreement - Confidential
                                  Schedule 1.13
<Page>

                                 SCHEDULE 2.4.3

                         DEVELOPMENT CANDIDATE CRITERIA


[***]

                           First Revised and Restated
             Research and Early Develoment Agreement - Confidential
                             Schedule 2.4.3 - Page 1
<Page>

                                    EXHIBIT A

          FORM OF LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT


                           First Revised and Restated
             Research and Early Develoment Agreement - Confidential
                                    Exhibit A
<Page>

                                    EXHIBIT B

                                 FORM OF INVOICE

                              [COMPANY Letterhead]

[Date]

Novartis Pharma AG
Zentraler Faktureneingang
Attn: Ms. R. Aschwanden
Lichtstrasse 35
CH - 4002 Basel
Switzerland

Dear Ms. Aschwanden

Re: [COMPANY] License Agreement for [PRODUCT]

This is an invoice requesting payment in connection the above-captioned
Agreement between [COMPANY] and Novartis Pharma AG.

Novartis Contract Code N DEG.:       [will be assigned within Novartis following
                                     execution]

Novartis Cost Centre:                630926 / 393120

SPECIFICATION:                       [PLEASE SPECIFY THE EVENT FOR WHICH THE
                                     INVOICE IS DUE, AND ADD ANY COPIES OF
                                     INVOICES FROM THIRD PARTIES IN CASE
                                     REIMBURSEMENT FOR THIRD PARTY WORK IS
                                     AGREED TO]

Amount and Currency:                 [self-explanatory]

Bank address and Account N DEG.:     [insert the name and address of the bank to
                                     which the payment should be sent and the
                                     account number to which it should be
                                     credited]

Sincerely yours,
[COMPANY]

                           First Revised and Restated
             Research and Early Develoment Agreement - Confidential
                                    Exhibit B
<Page>

                                    EXHIBIT A


              LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT


                                     BETWEEN


                       VERTEX PHARMACEUTICALS INCORPORATED



                                       AND


                               NOVARTIS PHARMA AG
<Page>

<Table>
<S>                                                                                                              <C>
ARTICLE I -- DEFINITIONS..........................................................................................2

ARTICLE II --  LICENSE...........................................................................................10
    2.1    Grant to NOVARTIS.....................................................................................10
    2.2    Grant to VERTEX.......................................................................................11
    2.3    Information Transfer..................................................................................11

ARTICLE III -- DEVELOPMENT.......................................................................................12
    3.1    Commencement of Development Program...................................................................12
    3.2    International Project Team............................................................................13
    3.3    Development Responsibility and Costs..................................................................14
    3.4    Regulatory Approvals..................................................................................15
    3.5    Assistance Rights.....................................................................................16
    3.6    Reasonable Efforts in Development.....................................................................17

ARTICLE IV --  MANUFACTURING AND SUPPLY..........................................................................17
    4.1    Supply of Bulk Drug Substance and Drug Product........................................................17
    4.2    [This section has been intentionally left blank.].....................................................17
    4.3    Formulation and Packaging.............................................................................18

ARTICLE V --   COMMERCIALIZATION.................................................................................18
    5.1    Marketing and Promotion...............................................................................18
    5.2    Global Brand Team.....................................................................................18
    5.3    [This section has been intentionally left blank.].....................................................19
    5.4    [This section has been intentionally left blank.].....................................................19
    5.5    Co-labeling...........................................................................................20
    5.6    Due Diligence.........................................................................................20

ARTICLE VI --  PAYMENTS..........................................................................................21
    6.1    Development Election Payment..........................................................................21
    6.2    Development Milestone Payments by NOVARTIS............................................................21
    6.3    Royalties.............................................................................................23
    6.4    [This section has been intentionally left blank.].....................................................24
    6.5    Sales Reports.........................................................................................24
    6.6    Withholding Tax.......................................................................................26

ARTICLE VII -- BACK-UP COMPOUNDS.................................................................................26

ARTICLE VIII -- INTELLECTUAL PROPERTY............................................................................27
    8.1    Patentable Inventions and Know-How....................................................................27
    8.2    Infringement Claims by Third Parties..................................................................28
    8.3    Infringement Claims Against Third Parties.............................................................30
    8.4    Notice of Certification...............................................................................31
    8.5    Patent Term Extensions................................................................................31

ARTICLE IX --  REPRESENTATIONS AND WARRANTIES....................................................................32
    9.1    Representations and Warranties of VERTEX..............................................................32
    9.2    Representations and Warranties of NOVARTIS............................................................33

ARTICLE X --   CONFIDENTIALITY...................................................................................34
    10.1   Undertaking...........................................................................................34
</Table>

      License, Development and Commercialization Agreement -- Confidential
<Page>

<Table>
<S>                                                                                                              <C>
    10.2   Exceptions............................................................................................35
    10.3   Publicity.............................................................................................36
    10.4   Survival..............................................................................................36

ARTICLE XI --  PUBLICATIONS......................................................................................36

ARTICLE XII -- DISPUTE RESOLUTION................................................................................38
    12.1   Governing Law, and Jurisdiction.......................................................................38
    12.2   Dispute Resolution Process............................................................................38

ARTICLE XIII -- TERM AND TERMINATION.............................................................................38
    13.1   Term..................................................................................................38
    13.2   Termination For Cause.................................................................................39
    13.3   Termination for Bankruptcy............................................................................39
    13.4   Termination by NOVARTIS...............................................................................39
    13.5   Effect of Termination.................................................................................40

ARTICLE XIV -- INDEMNIFICATION...................................................................................40
    14.1   Indemnification by VERTEX.............................................................................40
    14.2   Indemnification by NOVARTIS...........................................................................41
    14.3   Claims Procedures.....................................................................................41
    14.4   Compliance............................................................................................43
    14.5   Insurance.............................................................................................43

ARTICLE XV --  MISCELLANEOUS PROVISIONS..........................................................................43
    15.1   Notice of Pharmaceutical Side-Effects.................................................................43
    15.2   Waiver................................................................................................43
    15.3   Force Majeure.........................................................................................43
    15.4   Registration of License...............................................................................44
    15.5   Severability..........................................................................................44
    15.6   Government Acts.......................................................................................44
    15.7   Government Approvals..................................................................................44
    15.8   Assignment............................................................................................45
    15.9   Affiliates............................................................................................45
    15.10  Counterparts..........................................................................................45
    15.11  No Agency.............................................................................................45
    15.12  Notice................................................................................................46
    15.13  Headings..............................................................................................46
    15.14  Authority.............................................................................................47
    15.15  Entire Agreement......................................................................................47
    15.16  Inflation Adjustment..................................................................................47
    15.17  Invoice Requirement...................................................................................47
    15.18  Hardship..............................................................................................47

SCHEDULES
Schedule 1.12 -- List of Drug Product Candidates
Schedule 1.25 -- List of Major Markets
Schedule 1.29 -- NOVARTIS Patents
Schedule 1.44 -- VERTEX Patents
</Table>

      License, Development and Commercialization Agreement -- Confidential
<Page>

              LICENSE, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT


     This Agreement is made and entered into as of ________, _____ ( the
"Effective Date") between Vertex Pharmaceuticals Incorporated (hereinafter
"VERTEX"), a Massachusetts corporation with principal offices at 130 Waverly
Street, Cambridge, MA 02139-4242, and NOVARTIS PHARMA AG (hereinafter
"NOVARTIS"), a Swiss corporation with principal offices at Lichtstrasse 35,
CH-4056 Basel, Switzerland.

                                  INTRODUCTION

     WHEREAS, VERTEX and NOVARTIS are parties to a certain First Revised and
Restated Research Agreement dated January __, 2004 (the "Research Agreement")
which revised and restated a certain Research and Early Development Agreement
dated May 8, 2000 (the "Original Agreement"), under which VERTEX is attempting
to design novel, small-molecule compounds targeting the Kinase protein
superfamily; and

     WHEREAS, NOVARTIS may elect to develop and commercialize compounds proposed
by VERTEX under the Research Agreement; and

     WHEREAS, in accordance with the Research Agreement NOVARTIS has elected to
develop and commercialize the Drug Product Candidates designated on SCHEDULE
1.12 hereto, and the parties therefore wish to execute this License, Development
and Commercialization Agreement, which is identical in substance to the
agreement attached as Exhibit A to the Research Agreement, to memorialize the
provisions specific to development and commercialization of Drug Product
Candidates;

     WHEREAS, the parties have special rights and obligations with respect to
Back-up Compounds to the Drug Product Candidates (as defined in the Research
Agreement); and

     NOW THEREFORE, in consideration of the foregoing premises, the parties
agree as follows:

                                    ARTICLE I
                                   DEFINITIONS

For purposes of this Agreement, the terms defined in this Article 1 shall have
the following meanings whether used in their singular or plural forms. Use of
the singular shall include the plural and vice versa, unless the context
requires otherwise:

     1.1.      "AFFILIATE" shall mean, with respect to any Person, any other
Person which directly or indirectly, by itself or through one or more
intermediaries, controls, or is controlled

 License, Development and Commercialization Agreement -- Confidential -- Page 1
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by, or is under direct or indirect common control with, such Person. The term
"control" means the possession, direct or indirect, of the power to direct or
cause the direction of the management and policies of a Person, whether through
the ownership of voting securities, by contract or otherwise. Control will be
presumed if one Person owns, either of record or beneficially, more than 50% of
the voting stock of any other Person. For the avoidance of any doubt, the
Novartis Institute for Functional Genomics, Inc. and The Friedrich Miescher
Institute, as currently operated, are not Affiliates of NOVARTIS for the
purposes of this Agreement.

               1.1.1.    "CHANGE OF CONTROL" shall mean (a) a transaction which
results in the voting securities of VERTEX immediately prior to such transaction
ceasing to represent more than fifty percent (50%) of the combined voting power
of the surviving entity immediately after such transaction; (b) any Third Party
(other than any trustee or other fiduciary holding securities under an employee
benefit plan, or any corporation or other entity owned directly or indirectly by
the stockholders of such party in substantially the same portion as their
ownership of stock of such party) becoming the beneficial owner of more than
fifty percent (50%) of the combined voting power of the outstanding securities
of VERTEX; or (c) a sale to a Third Party of all or substantially all of the
business of VERTEX necessary for VERTEX's performance under this Agreement.

     1.2.      "GLOBAL BRAND TEAM" OR "GBT" shall have the meaning set forth in
Section 5.2 hereof; and "Back-up Compound" shall have the meaning set forth in
Section 1.1.1 of the Research Agreement.

     1.3.      [This section has been intentionally left blank.]

     1.4.      "BULK DRUG SUBSTANCE" shall mean a Drug Product Candidate in bulk
crystal, powder or other form suitable for incorporation in a Drug Product.

     1.5.      "CONTROLLED" shall mean the legal authority or right of a party
hereto to grant a license or sublicense of intellectual property rights to
another party hereto, or to otherwise disclose proprietary or trade secret
information to such other party, without breaching the terms of any agreement
with a Third Party, infringing upon the intellectual property rights of a Third
Party, or misappropriating the proprietary or trade secret information of a
Third Party.

     1.6.      [This section has been intentionally left blank.]

     1.7.      (a) "DEVELOPMENT CANDIDATE" shall have the meaning ascribed to it
in the Research Agreement.

               (b) "DEVELOPMENT ELECTION FEE" and "BACK-UP ELECTION FEE" shall
               each have the meaning ascribed to it in Section 6.1 hereof.

     1.8.      "DEVELOPMENT PLAN" shall have the meaning ascribed to it in
Section 3.2.2 hereof.

     1.9.      "DEVELOPMENT PROGRAM" shall mean activities associated with
development of a Drug Product Candidate which are conducted by or at the
direction of NOVARTIS after the Development Election has been exercised with
respect to that Drug Product Candidate, including but not limited to (a)
manufacture and formulation of Drug Product Candidates for use in pre-clinical,
non-clinical and clinical studies; (b) pre-clinical and non-clinical animal
studies

 License, Development and Commercialization Agreement -- Confidential -- Page 2
<Page>

performed in accordance with GLP (or the applicable equivalent); (c)planning,
implementation, evaluation and administration of human clinical trials; (d)
manufacturing process development, scale-up and commercial manufacture of Drug
Product; (e) preparation and submission of applications for Regulatory Approval;
and (f) post-market surveillance of approved drug indications, as required or
agreed as part of a marketing approval by any governmental regulatory authority.

     1.10.     [This Section has been intentionally left blank.]

     1.11.     "Drug Product" shall mean a finished dosage form which is
prepared from Bulk Drug Substance and is ready for administration to the
ultimate consumer as a pharmaceutical.

     1.12.     "DRUG PRODUCT CANDIDATE" shall mean any Development Candidate or
Drug Product Candidate Back-up Candidate listed from time to time on Schedule
1.12 hereof, as to which NOVARTIS has exercised the Development Election under
the Research Agreement and which has become a subject of this License Agreement
in accordance with the provisions thereof; and "Drug Product Candidate Back-up
Candidate" shall have the meaning set forth in Section 7.4 of this Agreement.

     1.13.     "EFFECTIVE DATE" shall mean the effective date of this Agreement
as set forth on the first page hereof.

     1.14.     [This section has been intentionally left blank.]

     1.15.     "FIELD" shall mean the treatment or prevention of conditions or
diseases in humans, principally by affecting a Kinase other than an Excluded
Kinase.

     1.16.     "FIRST COMMERCIAL SALE" shall mean the first sale of a Drug
Product by NOVARTIS or an Affiliate or sublicensee of NOVARTIS in a country in
the Territory following Regulatory Approval of the Drug Product in that country
or, if no such Regulatory Approval or similar marketing approval is required,
the date upon which the Drug Product is first commercially launched in such
country.

     1.17.     "FILING OUTSIDE THE U.S." shall mean any application or
regulatory filing to be made hereunder with a regulatory authority outside the
United States, for approval to manufacture and sell Drug Product(s) outside the
U.S., and any correspondence, approvals or governmental licenses relating
thereto.

     1.18.     [This section has been intentionally left blank.]

     1.19.     "GMP" shall mean the current Good Manufacturing Practice
regulations promulgated by the FDA, published at 21 CFR Part 210 et seq., as
such regulations may from time to time be amended, and such equivalent
regulations or standards of countries outside the United States as may be
applicable to activities conducted hereunder; and "GLP" shall mean the current
Good Laboratory Practices regulations promulgated by the FDA, published at 21
CFR Part 58, as such regulations may be from time to time amended, and such
equivalent regulations or standards of countries outside the United States as
may be applicable to activities conducted hereunder.

 License, Development and Commercialization Agreement -- Confidential -- Page 3
<Page>

     1.20.     "INDICATION" shall mean a recognized disease or condition, an
important manifestation of a disease or condition, or symptom associated with a
disease or syndrome for which use of a Drug Product is indicated, as would be
identified in the Drug Product's label under applicable FDA regulations or the
foreign equivalent thereof.

     1.21.     "IND" shall mean the investigational new drug application
relating to a Drug Product Candidate filed with the FDA pursuant to 21 CFR Part
312, including any amendments thereto. References herein to IND shall include,
to the extent applicable, any comparable Filing(s) Outside the U.S. (such as a
CTX in the European Union).

     1.22.     "INTERNATIONAL PROJECT TEAM" or "IPT" shall have the meaning set
forth in Section 3.2.1 hereof.

     1.23.     "JOINT STEERING COMMITTEE" or "JSC" shall have the meaning set
forth in Section 2.6 of the Research Agreement.

     1.24.     "KNOW-HOW" means all proprietary material and information
including data, technical information, know-how, experience, inventions,
discoveries, trade secrets, compositions of matter and methods, whether
currently existing or developed or obtained during the course of this Agreement
and whether or not patentable or confidential, that are now Controlled by a
Party or its Affiliates and that relate to the development, utilization,
manufacture or use of any Drug Product Candidate or Drug Product, including but
not limited to processes, techniques, methods, products, materials and
compositions; provided however, that for the purposes of the definition of
VERTEX Know-How only, the term "Know-How" shall not include VERTEX's general
drug design technology, whether in software or hardware, tangible or intangible,
form; and "Lead Period" shall mean the period starting on date this Agreement is
effective with respect to a particular Drug Product Candidate and ending on the
second anniversary thereafter.

     1.25.     "MAJOR MARKETS" shall mean those countries listed on Schedule
1.25 hereto.

     1.26.     "MANUFACTURING COST" shall mean [***].

     1.27.     "NET SALES" with respect to any Drug Product shall mean the gross
amount invoiced by NOVARTIS and any NOVARTIS Affiliate, licensee or sublicensee
for that Drug Product sold to Third Parties in bona fide, arms-length
transactions, less [***]; all as determined in accordance with NOVARTIS' usual
and customary accounting methods, which are in accordance with generally
accepted accounting principles (GAAP).

               1.27.1. In the case of any sale or other disposal of a Drug
Product between or among NOVARTIS and its Affiliates, licensees and
sublicensees, for resale, Net Sales shall be calculated as above only on the
value charged or invoiced on the first arm's-length sale thereafter to a Third
Party;

               1.27.2. In the case of any sale which is not invoiced or is
delivered before invoice, Net Sales shall be calculated at the time of shipment
or when the Drug Product is paid for, if paid for before shipment or invoice;

               1.27.3. In the case of any sale or other disposal for value,
such as barter or counter-trade, of any Drug Product, or part thereof, other
than in an arm's length transaction

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<Page>

exclusively for money, Net Sales shall be calculated as above on the value of
the consideration received or the fair market price (if higher) of the Drug
Product in the country of sale or disposal;

               1.27.4. In the event the Drug Product is sold in a finished
dosage form containing the Drug Product in combination with one or more other
active ingredients (a "Combination Product"), the Net Sales of the Drug Product,
for the purposes of determining royalty payments, shall be determined by [***].

     1.28.     "NOVARTIS KNOW-HOW" shall mean all Know-How of NOVARTIS.

     1.29.     "NOVARTIS PATENTS" shall mean any Patents Controlled by NOVARTIS
or any of its Affiliates claiming Bulk Drug Substance, a Drug Product Candidate
or a Drug Product, or a formulation or prodrug thereof, discovered or identified
by NOVARTIS or its Affiliates during the course of the Research Program or a
Development Program, or a method of making or using Bulk Drug Substance, a Drug
Product Candidate or a Drug Product, or a prodrug thereof, or an improvement to
the subject matter of a Patent covering any of the foregoing. A list of NOVARTIS
Patents is appended hereto as Schedule 1.29 and will be updated periodically to
reflect additions thereto during the term of this Agreement. NOVARTIS shall keep
VERTEX periodically informed in writing of all NOVARTIS Patents.

     1.30.     "NOVARTIS TECHNOLOGY" shall mean all NOVARTIS Patents and all
NOVARTIS Know-How which is applied by NOVARTIS to the development, manufacture
or use of Bulk Drug Substance, a Drug Product Candidate or a Drug Product.

     1.31.     "PATENTS" means all existing patents and patent applications and
all patent applications hereafter filed, including any continuation,
continuation-in-part, division, provisional or any substitute applications, any
patent issued with respect to any such patent applications, any reissue,
reexamination, renewal or extension (including any supplementary protection
certificate) of any such patent, and any confirmation patent or registration
patent or patent of addition based on any such patent, and all foreign
counterparts of any of the foregoing.

     1.32.     "PERSON" shall mean any individual, corporation, partnership,
association. joint-stock company, trust, unincorporated organization or
government or political subdivision thereof.

     1.33.     "PIVOTAL REGISTRATION STUDY" shall mean a human clinical trial
conducted for inclusion in (i) that portion of the FDA submission and approval
process which provides for the continued trials of a Drug Candidate on
sufficient numbers of patients to generate safety and efficacy data to support
Regulatory Approval in the proposed therapeutic indication, as more fully
defined in 21 CFR. Section 312.21(c), and (ii) equivalent submissions with
similar requirements in other countries.

     1.34.     "REGULATORY APPROVAL" shall mean, with respect to any country,
all authorizations by the appropriate governmental entity or entities necessary
for commercial sale of a Drug Product in that country including, without
limitation and where applicable, approval of labeling, price, reimbursement and
manufacturing. "Regulatory Approval" in the United States shall mean final
approval of a new drug application pursuant to 21 CFR Section 314, permitting
marketing of the applicable Drug Product in interstate commerce in the United
States. "Regulatory Approval" in the European Union shall mean final approval of
a Marketing

 License, Development and Commercialization Agreement -- Confidential -- Page 5
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Authorization Application pursuant to Council Directive 75/319/EEC, as amended,
or Council Regulation 2309/93/EEC, as amended.

     1.35.     "RESEARCH AGREEMENT" shall mean that certain First Revised and
Restated Research and Early Development Agreement between VERTEX and NOVARTIS
dated February 3, 2004.

     1.36.     [This section has been intentionally left blank.]

     1.37.     [This section has been intentionally left blank.] =

     1.38.     "Technology" shall mean VERTEX Technology and NOVARTIS
Technology.

     1.39.     "Territory" shall mean all the countries in the world.

     1.40.     "Third Party" shall mean any person or entity which is not a
party or an Affiliate of any party to this Agreement.

     1.41.     [This section has been intentionally left blank.]

     1.42.     "VALID PATENT CLAIM" shall mean either (a) a claim of an issued
and unexpired Patent which has not been revoked or held permanently
unenforceable or invalid by a decision of a court or other governmental agency
of competent jurisdiction, unappealable or unappealed within the time allowed
for appeal, and which has not been admitted to be invalid or unenforceable
through reissue or disclaimer or otherwise, or (b) a claim of a pending patent
application which claim was filed in good faith and has not been abandoned or
finally disallowed without the possibility of appeal or refiling of said
application.

     1.43.     "VERTEX KNOW-HOW" shall mean all Know-How of VERTEX.

     1.44.     "VERTEX PATENTS" shall mean any Patents Controlled by VERTEX or
any of its Affiliates claiming Bulk Drug Substance, a Drug Product Candidate or
a Drug Product, or a formulation or prodrug thereof, discovered or identified by
VERTEX or its Affiliates during the course of the Research Program and the
Development Program, or a method of making or using Bulk Drug Substance, a Drug
Product Candidate or a Drug Product, or a prodrug thereof, or an improvement to
the subject matter of a Patent covering any of the foregoing. A list of VERTEX
Patents is appended hereto as Schedule 1.44 and will be updated periodically to
reflect additions thereto during the term of this Agreement.

     1.45.     "VERTEX TECHNOLOGY" shall mean all VERTEX Patents and all VERTEX
Know-How.

     1.46.     The term "European Union" shall mean those countries which are
now or later become members of the European Union.

Capitalized terms used but not otherwise defined herein which are defined in the
Research Agreement shall have the meaning ascribed to them therein.

                                   ARTICLE II
                                     LICENSE

     2.1.      GRANT TO NOVARTIS.

 License, Development and Commercialization Agreement -- Confidential -- Page 6
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                  (a) Subject to the other provisions of this Agreement, VERTEX
hereby grants to NOVARTIS an exclusive worldwide license under VERTEX Technology
to the extent useful to permit NOVARTIS to carry out its rights and obligations
set forth in this Agreement and to develop, manufacture, have manufactured,
market, use, sell and import for sale, as provided herein, Bulk Drug Substance,
Drug Product Candidates and Drug Products worldwide. NOVARTIS shall have the
right to sublicense under this Agreement. Subject to the provisions of this
Agreement, VERTEX shall have the right to use VERTEX Technology to discharge its
obligations and exercise its rights under this Agreement. VERTEX retains all
rights to VERTEX Technology except to the extent explicitly granted to NOVARTIS
hereunder.

                  (b) NOVARTIS may subcontract its rights to manufacture Bulk
Drug Substance, Drug Product Candidates, and Drug Product and may contract with
reputable organizations to conduct or assist in the conduct of human clinical
trials and the evaluation of trials data, after prior notice to, but without the
consent of, VERTEX. NOVARTIS shall be responsible to VERTEX for the performance
of any of its sublicensees or subcontractors under any provisions of this
Agreement for which NOVARTIS is responsible. NOVARTIS shall not permit any
subcontractors or sublicensees to use VERTEX Technology without provisions
safeguarding confidentiality at least equivalent to those provided in this
Agreement. Any such provisions will allow VERTEX the right to directly enforce
the obligations of confidentiality with respect to VERTEX Technology in
possession of the Third Party.

                  (c) [***]

     2.2.      GRANT TO VERTEX. Subject to the other provisions of this
Agreement, NOVARTIS hereby grants to VERTEX a non-exclusive, worldwide license
or (as appropriate) sublicense under NOVARTIS Technology, only to the extent
necessary to permit VERTEX to carry out the activities which it is permitted to
undertake in this Agreement. VERTEX shall not sublicense such license to the
NOVARTIS Technology without the consent of NOVARTIS (which shall not be
unreasonably withheld). Any permitted sublicense will contain provisions
safeguarding confidentiality at least equivalent to those provided in this
Agreement, which will allow NOVARTIS the right to directly enforce the
obligations of confidentiality with respect to NOVARTIS Technology in possession
of the Third Party. NOVARTIS retains all rights to NOVARTIS Technology except to
the extent explicitly granted to VERTEX hereunder.

     2.3.      Information Transfer.
                  (a)  [***]

                  (b)  [***]

                  (c)  [***]

 License, Development and Commercialization Agreement -- Confidential -- Page 7
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                                   ARTICLE III
                                   DEVELOPMENT

     3.1.      COMMENCEMENT OF DEVELOPMENT PROGRAM. NOVARTIS shall promptly and
diligently commence and pursue a Development Program with respect to each Drug
Product Candidate as soon as practicable after exercise by NOVARTIS of its
Development Election with respect to that Drug Product Candidate.

     3.2.      INTERNATIONAL PROJECT TEAM.

               3.2.1.  FORMATION AND RESPONSIBILITIES. As soon as practicable
                       after the exercise by NOVARTIS of its Development
                       Election with respect to a Drug Product Candidate,
                       NOVARTIS will establish an International Project Team
                       ("IPT") which shall include one representative designated
                       by VERTEX from time to time; provided, however, an IPT
                       shall no longer include a representative designated by
                       VERTEX in case of a Change of Control of VERTEX.
                       Additional IPT's, which shall also include one VERTEX
                       representative, may be established from time to time in
                       connection with the development of additional Drug
                       Product Candidates. The IPT (or its successor
                       organization, as designated by NOVARTIS) will be the
                       principal organization through which the development of a
                       Drug Product Candidate is planned, administered,
                       evaluated and completed, subject to appropriate review
                       and approval at senior management levels as required by
                       NOVARTIS from time to time. In addition to the VERTEX
                       member, the IPT will typically have members from the
                       various functional groups (e.g., research, preclinical
                       safety, clinical, regulatory, marketing) which are or
                       will be expected to be involved in development and launch
                       of the Drug Product Candidate and Drug Product. NOVARTIS
                       will appoint the IPT Chair. The IPT will typically meet
                       every four to six weeks, depending on the level of
                       current development activity, and will be responsible for
                       preparation and implementation of the Development Plan
                       described in Section 3.2.2 below with respect to each
                       Drug Product Candidate.

               3.2.2.  DEVELOPMENT PLAN. The IPT shall prepare and oversee the
                       implementation of the overall Development Plan for each
                       Drug Product Candidate. The Development Plan shall, among
                       other things, detail, schedule and fully describe the
                       proposed toxicology studies, clinical trials, regulatory
                       plans, clinical trial and commercial material
                       requirements, and process development and manufacturing
                       plans for each Drug Product Candidate, along with
                       relevant budget information for the described items, and
                       will outline the key elements involved in obtaining
                       Regulatory Approval in each country where the Drug
                       Product is to be marketed. The parties expect that
                       development tasks will be advanced in parallel rather
                       than serially where practicable and appropriate, if doing
                       so would be likely to advance the ultimate date of
                       Regulatory Approval and launch and is otherwise
                       commercially reasonable.

 License, Development and Commercialization Agreement -- Confidential -- Page 8
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               3.2.3.  MEETING MATERIALS. The IPT will consider all information
                       that is material to an assessment of the status,
                       direction and progress of the Development Program,
                       including all clinical trials protocols, data and
                       reports. The IPT Leader will ensure that full and
                       complete minutes are prepared and distributed to each
                       member of the IPT promptly after each meeting. Those
                       minutes shall contain a full report on the activities of
                       the IPT during its meeting. VERTEX's representative on
                       the IPT will receive all documents and information
                       distributed or communicated to members of the IPT
                       generally, and may review copies of all other information
                       relative to the development of a Drug Product Candidate
                       unless the IPT Leader denies access to that information
                       for good reason.

               3.2.4.  [This section has been intentionally left blank.]

     3.3.      DEVELOPMENT RESPONSIBILITY AND COSTS. Except as provided in
Section 3.5 below, NOVARTIS will have sole responsibility for, and bear the cost
of conducting, the Development Program with respect to each Drug Product
Candidate.

     3.4.      REGULATORY APPROVALS. NOVARTIS shall be solely responsible for
preparing and submitting registration dossiers for Regulatory Approval of Drug
Product Candidates in the Territory.

               3.4.1.  NOVARTIS OWNERSHIP. All Regulatory Approvals shall be
                       held by and in the name of NOVARTIS, and NOVARTIS shall
                       own all submissions in connection therewith, provided
                       that VERTEX shall have a right of reference to all or any
                       part of the submissions if the "Assistance Rights" become
                       effective under Section 3.5 hereof.

               3.4.2.  PRINCIPAL INTERFACE. All formulary or marketing approvals
                       shall also be obtained by and in the name of NOVARTIS,
                       and NOVARTIS will be the principal interface with and
                       will otherwise handle all interactions with regulatory
                       agencies concerning any Drug Product including, to the
                       extent legally possible, being the sole contact with such
                       agencies, subject to the rights of VERTEX under Section
                       3.4.3.

               3.4.3.  REGULATORY MEETINGS. To the extent not prohibited by law
                       or regulation, VERTEX shall have the right, after
                       consultation with NOVARTIS and unless VERTEX's presence
                       would impede the regulatory approval process, to have one
                       representative participate in all material meetings
                       between representatives of NOVARTIS and any of the FDA,
                       the EMEA and Koseisho (MHW Japan).

                   (a) NOVARTIS will undertake to provide VERTEX with
information reasonably in advance of the meeting sufficient to ensure that the
VERTEX representative is adequately informed about the issues to be presented at
any such meeting.

                   (b) VERTEX may request NOVARTIS to provide VERTEX with a
copy of any correspondence between the FDA, the EMEA and Koseisho that relates
to any material issues involving Regulatory Approval of a Drug Product
Candidate, and NOVARTIS shall provide that information upon request, unless
NOVARTIS has good reason to withhold any such correspondence, in which case it
will notify VERTEX of that reason promptly.

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                   (c) Notwithstanding the foregoing, NOVARTIS will have sole
discretion as to the regulatory strategy and decision-making for any Drug
Product Candidate or Drug Product.

     3.5.      Assistance Rights. [***]

               3.5.1.  [***]

               3.5.2.  If VERTEX pursues its Assistance Rights:

                   (a) REGULATORY ACTIONS. NOVARTIS will continue to make any
necessary and appropriate regulatory filings with respect to the Development
Work and will, if required for VERTEX to exercise its Assistance Rights
effectively, transfer to VERTEX at VERTEX's expense any IND material (or
equivalents thereof) relevant to such Development Work.

                   (b) MANUFACTURE OF CLINICAL SUPPLY OF DRUG PRODUCT
CANDIDATE. NOVARTIS will supply VERTEX (for up to two years) with the necessary
clinical supply of Drug Product Candidate required to perform such Development
Work in accordance with NOVARTIS' then current scale of manufacturing at
NOVARTIS' Manufacturing Cost and upon such other reasonable and customary terms
as to shipment, delivery and similar matters as may be agreed.

                   (c) MILESTONES. If NOVARTIS elects to resume the Development
Program for a Drug Product Candidate, it will provide VERTEX with ninety (90)
days prior notice thereof, and will reimburse VERTEX for the actual direct cost
of the Development Work of good quality, if such work conforms with the
requirements of the relevant Development Plan. NOVARTIS will pay VERTEX interest
on the reimbursable costs incurred by VERTEX in the conduct of the Development
Work, at a rate compounded quarterly equal to the thirty-day London InterBank
Offered Rate ("LIBOR") for the local currency in which payment is made, as
quoted in THE FINANCIAL TIMES as determined on the date the Development Work is
first undertaken by VERTEX and on the last Business Day of each calendar quarter
thereafter.

     3.6.      REASONABLE EFFORTS IN DEVELOPMENT. NOVARTIS will use diligent,
commercially reasonable efforts consistent with those used by NOVARTIS for its
own compounds of similar commercial potential to develop Drug Product Candidates
into Drug Products. NOVARTIS will promptly notify VERTEX in writing if it should
determine that development of any Drug Product Candidate or Drug Product is not
technically feasible or commercially justifiable, specifying in reasonable
detail the reasons for that determination.

                                   ARTICLE IV
                            MANUFACTURING AND SUPPLY

     4.1.      Supply of Bulk Drug Substance and Drug Product. NOVARTIS will be
responsible for manufacturing and supply of all Bulk Drug Substance, Drug
Product Candidates and Drug Product as necessary for the conduct of the
Development Plan and for all commercial purposes in the Territory. Pursuant to
the provisions of Section 4.7 of the Research Agreement, the parties will agree
on reasonable and appropriate measures by which manufacturing previously being
undertaken by VERTEX shall be transitioned to NOVARTIS following the exercise of
its Development Election with respect to a particular Drug Product Candidate.
The objective of both parties will be to accomplish a smooth and timely
transition. Any Bulk Drug

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Substance provided to NOVARTIS during the transition period will be supplied at
VERTEX's reasonable Manufacturing Cost.

     4.2.      [This section has been intentionally left blank.]
                                                                   =

     4.3.      FORMULATION AND PACKAGING. In all events, NOVARTIS will be
responsible for formulation and packaging of Drug Products.

                                    ARTICLE V
                                COMMERCIALIZATION

     5.1.      MARKETING AND PROMOTION. NOVARTIS shall have exclusive rights to
market, sell and distribute all Drug Products in the Territory. NOVARTIS will
book all sales of Drug Products and will report those sales to VERTEX as
specified in Section 6.5 of this Agreement.

     5.2.      GLOBAL BRAND TEAM. Not later than six months prior to the
commencement of Phase III Clinical Trials for any Drug Product Candidate,
NOVARTIS will form a Global Brand Team ("GBT"), which will include one
representative designated by VERTEX; provided, however, [***]. Additional GBT's,
which shall also include one VERTEX representative, may be established from time
to time in connection with the marketing of additional Drug Product Candidates.
The GBT (or its successor organization, as designated by NOVARTIS) will be the
principal organization through which the marketing of a Drug Product is planned,
administered, evaluated and effected, subject to appropriate review at senior
management levels as required by NOVARTIS. NOVARTIS will appoint the chair of
the GBT, who will normally be the Brand Director. The GBT will periodically meet
as necessary, depending on the level of marketing activity at the time.

               5.2.1.  MARKETING PLANS. The Global Brand Team will prepare and
                       oversee the implementation of a detailed marketing plan
                       (a "Marketing Plan") for the launch of each Drug Product,
                       addressing the overall branding and branding elements as
                       well as the key promotional product claims. The GBT will
                       select an external agency or agencies which will be
                       charged with the execution of some components of the
                       Marketing Plan. The Marketing Plan will contain among
                       other things budgets, schedules, product positioning,
                       pricing, market research plans and results and other
                       customary planning and marketing material with respect to
                       marketing and launch of the Drug Product. The Marketing
                       Plan will be periodically updated to reflect changes in
                       market information, sales performance and forecasts,
                       sales force deployment, communication plans and
                       information concerning competition and competitors.

               5.2.2.  LOCAL PRODUCT TEAMS. Local Product Teams will be
established in each country to prepare and execute the product launch for a Drug
Product within the framework of the Marketing Plan. .

               5.2.3.  CAMPAIGNS AND PROMOTIONAL MATERIALS. The GBT will review
                       all general product campaigns (including target audience
                       and principal messages) and may from time to time review
                       the principal promotional material to be used in
                       connection with the marketing and sale of a Drug Product.

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               5.2.4.  [This section has been intentionally left blank.]

     5.3.      [This section has been intentionally left blank.]

     5.4.      [This section has been intentionally left blank.]

     5.5.      CO-LABELING. To the extent not prohibited by law or regulation
and subject to any required Regulatory Approval, Drug Products (including
labels, packaging and inserts) and all promotional materials for the same, sold
in North America, the countries of the European Union and Japan will bear both
NOVARTIS' and VERTEX's company names and logos with equal prominence (including
equal sized type face), or if equal prominence is prohibited by law, with such
prominence as may otherwise be permitted by law. To the extent not prohibited by
law or regulation and subject to any required Regulatory Approval, Drug Products
(including labels, packaging and inserts) and all promotional materials for the
same, sold in the rest of the world will include VERTEX's company name (in the
English alphabet) and logo with the designation: "under license from"; provided,
however, that this provision shall no longer apply in case of a Change of
Control of VERTEX. Any trademark for a Drug Product will be selected by, and
will be the property of, NOVARTIS.

               5.5.1.  REVIEW OF REGULATORY FILINGS. NOVARTIS will permit VERTEX
                       to review all material regulatory filings which relate to
                       product labeling, and all proposed labels, packaging,
                       package inserts, and promotional materials required under
                       the Agreement to bear VERTEX's name, if permitted by law,
                       prior to the filing of any such materials with any
                       regulatory authority; provided, however, that this
                       provision shall no longer apply in case of a Change of
                       Control of VERTEX.

               5.5.2.  REGULATORY COMMUNICATIONS.

                   (a) NOVARTIS will permit VERTEX to participate with NOVARTIS
in material communications with regulatory officials which concern the matters
referenced in this Section 5.5; provided, however, [***].

                   (b) NOVARTIS will immediately inform VERTEX of any material
regulatory communications received by NOVARTIS which might operate to restrict
VERTEX's rights under this Section 5.5.2, and will cooperate with any reasonable
request of VERTEX aimed at facilitating approval by a regulatory authority for
co-labeling consistent with this provision.

     5.6.      DUE DILIGENCE. NOVARTIS shall use diligent and commercially
reasonable efforts consistent with the requirements of the Development Program
and sound and reasonable business practices and judgment to effect introduction
of Drug Products into Major Markets as soon as reasonably practicable, devoting
the same degree of attention and diligence to such efforts that it devotes to
such activities for other of its products of comparable market potential.
Following the First Commercial Sale of a Drug Product and until the expiration
of this Agreement, NOVARTIS shall endeavor to keep Drug Products reasonably
available to the public in each of the Major Markets. NOVARTIS shall promptly
notify VERTEX if it shall determine that the marketing and sale of a Drug
Product in any country is not commercially reasonable or economically profitable
or if for other unforeseen reasons further commercial support of the Drug
Product in certain territories is no longer prudent or practical. In determining
whether NOVARTIS is in compliance with the foregoing provisions, there shall be
taken into account the

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normal course of assertive drug development programs in the pharmaceutical
industry conducted with sound and reasonable business practices and judgment.

                                   ARTICLE VI
                                    PAYMENTS

     6.1.      DEVELOPMENT ELECTION PAYMENT. NOVARTIS will pay to VERTEX a
milestone payment in the amount of [***] (a "Development Election Fee") each
time NOVARTIS exercises its Development Election with respect to a Development
Candidate. Each time NOVARTIS exercises its Development Election under Section
4.1 of the Research Agreement with respect to a Compound which is a Back-up
Compound to a Drug Product Candidate, NOVARTIS will pay to VERTEX a milestone
payment in the amount of [***] (the "Back-up Election Fee"); [***]

     6.2.      Development Milestone Payments by NOVARTIS.

               6.2.1.  NOVARTIS will make the following payments to VERTEX upon
                       the achievement of any of the following milestones with
                       respect to a Drug Product Candidate:

                                [***]                  [***]
                       ---------------------------------------------
                       [***]                                 [***]
                       ---------------------------------------------
                       [***]                                 [***]
                       ---------------------------------------------
                       [***]                                 [***]
                       ---------------------------------------------
                       [***]                                 [***]
                       ---------------------------------------------
                       [***]                                 [***]
                       ---------------------------------------------

               6.2.2.  [This section has been intentionally left blank.]

               6.2.3.  All payments shall be made by wire transfer in United
                       States dollars ("Dollars") to the credit of such bank
                       account as may be designated by VERTEX in writing to
                       NOVARTIS. Any payment which falls due on a date which is
                       a Saturday, Sunday or a legal holiday in the Commonwealth
                       of Massachusetts may be made on the next succeeding day
                       which is not a Saturday, Sunday or a legal holiday in the
                       Commonwealth.

               6.2.4.  If a Drug Product Candidate is abandoned during the term
of this Agreement for any scientific or medical reasons after any one or more of
the foregoing milestone payments are made, and if a Back-up Compound to that
Drug Product Candidate is developed to replace the abandoned Drug Product
Candidate for the same Indications, then no milestone

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payment shall be required with respect to the Back-up Compound to the extent
that that milestone payment has already been made with respect to the abandoned
Drug Product Candidate.

     6.3.      ROYALTIES.  NOVARTIS  shall pay to VERTEX the  following  annual
royalties on Net Sales of each Drug Product in the Territory.
               [***]

               6.3.1.  Third Party Royalties: If NOVARTIS is required to pay
                       royalties to any Third Party in order to exercise its
                       rights to sell a Drug Product in a country, then
                       [***]payable to such Third Party in any calendar quarter
                       for such Drug Product in such country shall be deductible
                       from the royalties payable to VERTEX under this Agreement
                       in respect of sales of that Drug Product in such country
                       for the same calendar quarter, provided that in no event
                       shall the net royalty rate payable fall below [***], as a
                       result of the application of this Sections 6.3.1 and
                       6.3.2.

               6.3.2.  Unlicensed Competition: If in any country a Third Party
                       sells a pharmaceutical product which is a "generic
                       version" of a Drug Product being sold in that country (a
                       "Third Party Product") -- where "generic version" means a
                       pharmaceutical product (other than a product originally
                       sold as a Drug Product) that includes the same active
                       ingredient as that used in a Drug Product -- then for the
                       period in which the sales of such Third Party Product in
                       such country are at least [***], the royalties payable to
                       VERTEX by NOVARTIS on sales of such Product in such
                       country for such period shall be [***] in Section 6.3 ,
                       but in no event shall the royalties owed for such Drug
                       Product in such country, when combined with any royalty
                       reduction provided under Section 6.3.1 hereof, reduce the
                       royalties payable on Net Sales of such Drug Product in
                       that country by more than [***]

     6.4.      [This section has been intentionally left blank.]

     6.5.      SALES REPORTS.
               (a)     During the term of this Agreement and after the First
Commercial Sale of a Drug Product, NOVARTIS shall furnish or cause to be
furnished to VERTEX on a quarterly basis a written report or reports covering
each calendar quarter (each such calendar quarter being sometimes referred to
herein as a "reporting period") showing (i) the Net Sales of each Drug Product
in each country in the world during the reporting period by NOVARTIS and each
Affiliate and sublicensee; (ii) the royalties, payable in Dollars, which shall
have accrued under Section 6.3 hereof in respect of such sales and the basis of
calculating those royalties; (iii) withholding taxes, if any, required by law to
be deducted in respect of any such sales; (iv) the exchange rates used in
converting into Dollars, from the currencies in which sales were made, any
payments due which are based on Net Sales; and (v) dispositions of Drug Products
other than pursuant to sale for cash. With respect to sales of Drug Products
invoiced in Dollars, the Net Sales amounts and the amounts due to VERTEX
hereunder shall be expressed in Dollars. With respect to sales of Drug Products
invoiced in a currency other than Dollars, the Net Sales

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and amounts due to VERTEX hereunder shall be expressed in the domestic currency
of the party making the sale, together with the Dollar equivalent of the amount
payable to VERTEX, calculated using NOVARTIS' then-current standard exchange
rate methodology for the translation of foreign currency sales into U.S.
dollars. In each report the methodology will be disclosed, will be identical to
that employed by NOVARTIS, generally, in its external financial reporting, as
reviewed and approved by its independent auditors and will be in conformity with
NOVARTIS' usual and customary general accounting principles consistently
applied. If any sublicensee makes any sales invoiced in a currency other than
its domestic currency, the Net Sales shall be converted to its domestic currency
in accordance with the sublicensee's normal accounting principles. NOVARTIS
shall furnish to VERTEX appropriate evidence of payment of any tax or other
amount required by applicable laws or regulations to be deducted from any
royalty payment, including any tax or withholding levied by a foreign taxing
authority in respect of the payment or accrual of any royalty. Reports shall be
due on the thirtieth (30th) day following the close of each reporting period,
although NOVARTIS shall also provide VERTEX with a "flash" report of Net Sales,
only, within ten (10) business days after the end of each month. NOVARTIS shall
keep accurate records in sufficient detail to enable the amounts due hereunder
to be determined and to be verified by VERTEX.

               (b)     Amounts shown to have accrued by each sales report
provided for under subsection 6.5(a), above, shall be due and payable on the
date such sales report is due.

               (c)     All payments shall be made in Dollars. If at any time
legal restrictions prevent the prompt remittance of any payments with respect to
any country of the Territory where Drug Products are sold, NOVARTIS or its
sublicensees shall have the right and option to make such payments by depositing
the amount thereof in local currency to VERTEX's account in a bank or depository
in such country.

               (d)     Upon the written request of VERTEX, at VERTEX's expense
and not more than once in or in respect of any calendar year, NOVARTIS shall
permit an independent accountant of national prominence selected by VERTEX, to
have access during normal business hours to those records of NOVARTIS as may be
reasonably necessary to verify the accuracy of the sales reports furnished by
NOVARTIS pursuant to this Section 6.5, in respect of any calendar year ending
not more than thirty-six (36) months prior to the date of such notice. NOVARTIS
shall include in each sublicense entered into by it pursuant to this Agreement a
provision requiring the sublicensee to keep and maintain adequate records of
sales made pursuant to such sublicense and to grant access to such records by
the aforementioned independent accountant for the reasons specified in this
Section 6.5. Upon the expiration of thirty-six (36) months following the end of
any calendar year, the calculation of amounts payable with respect to such
fiscal year shall be binding and conclusive upon VERTEX, and NOVARTIS and its
sublicensees shall be released from any liability or accountability with respect
to payments for such year. The report prepared by such independent accountant, a
copy of which shall be sent or otherwise provided to NOVARTIS by such
independent accountant at the same time it is sent or otherwise provided to
VERTEX, shall contain the conclusions of such independent accountant regarding
the audit and will specify that the amounts paid to VERTEX pursuant thereto were
correct or, if incorrect, the amount of any underpayment or overpayment. If such
independent accountant's report shows any underpayment, NOVARTIS shall remit or
shall cause its sublicensees to remit to VERTEX within thirty (30) days after
NOVARTIS' receipt of such report, (i) the amount of such underpayment and (ii)
if such underpayment exceeds [***] owed for the calendar year then being

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audited, the reasonable and necessary fees and expenses of such independent
accountant performing the audit, subject to reasonable substantiation thereof.
Any overpayments shall be fully creditable against amounts payable in subsequent
payment periods. VERTEX agrees that all information subject to review under this
Section 6.5 or under any sublicense agreement is confidential and that VERTEX
shall retain and cause its accountant to retain all such information in
confidence.

               (e)     In case of any delay in payment by NOVARTIS to VERTEX not
occasioned by Force Majeure, interest at the rate of [***], assessed from the
thirty-first day after the due date of the payment, shall be due from NOVARTIS
upon prior written notice.

     6.6.      WITHHOLDING TAX. If during the term of this Agreement,
withholding tax should be required by law to be deducted from any payments
required to be made by NOVARTIS to VERTEX hereunder, the parties will agree upon
an equitable division of liability for any sum which is withheld and for which
VERTEX is not compensated or reimbursed by way of usable tax credits or
otherwise. In that connection VERTEX at NOVARTIS' request shall sign a usual and
customary exemption application and in addition shall apply for a tax refund at
the request of NOVARTIS from any tax authority to which NOVARTIS has paid
withholding tax on account of any payments made by NOVARTIS to VERTEX hereunder.

                                   ARTICLE VII
                                BACK-UP COMPOUNDS

               Notwithstanding the provisions under the Research Agreement
with respect to Back-up Compounds and for the sake of clarity, it is reminded
that the parties agreed the following with respect to Back-up Compounds in
Section 4.5 of the Research Agreement.

7.1  VERTEX RESTRICTIONS ON NOMINATION AND DEVELOPMENT. So long as NOVARTIS is
     using commercially reasonable efforts with respect to the development of a
     particular Drug Product Candidate or the commercialization of a particular
     Drug Product, pursuant to Sections 3.6 and 5.6 hereof, VERTEX will not (i)
     propose a Compound for development under the License Agreement which is a
     Back-up Compound with respect to that Drug Product Candidate or Drug
     Product, or (ii) until after the period starting on the date on which
     NOVARTIS has exercised its Development Election for a particular Drug
     Product Candidate and ending [***] (the "Lead Period"), commence
     development of that Back-up Compound either directly or together with or
     through an Affiliate or a Third Party.

7.2  TERMINATION OF DEVELOPMENT OR COMMERCIALIZATION. If, prior to the end of
     the Lead Period with respect to a particular Drug Product or Drug Product
     Candidate, pursuant to Sections 3.6 and 5.6 hereof, NOVARTIS ceases to use
     commercially reasonable efforts to develop or commercialize that Drug
     Product Candidate or Drug Product, then the restrictions on nomination and
     development referenced in Section 7.1 above will no longer apply with
     respect to Back-up Compounds for that Drug Product Candidate or Drug
     Product unless NOVARTIS, without delay, commences another Development
     Program under the License Agreement with another Compound (a "Replacement
     Candidate") targeting the same Kinase, which Replacement Candidate is a
     Back-up Compound

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     associated with the discontinued Drug Product Candidate or Drug Product,
     and NOVARTIS shall have the right to select for this purpose any such
     Back-up Compound by providing VERTEX with notice of its Development
     Election in this regard. Any such Back-up Compound for which NOVARTIS has
     exercised its Development Election under this Section 7.2 shall hereafter
     be a Drug Product Candidate subject to the terms and conditions of this
     Agreement.

7.3. TERMINATION OF RIGHTS TO BACK-UP COMPOUNDS. A Back-up Compound will no
     longer be subject to NOVARTIS' Development Election under the Research
     Agreement after the end of the Lead Period applicable to that Back-up
     Compound, except for Back-up Compounds which (i) subject to Section 7.1
     above, VERTEX has proposed for development on or before the Final
     Termination Date, and as to which NOVARTIS has exercised its Development
     Election hereunder; or (ii) have been or will be selected by NOVARTIS for
     development before the end of the applicable Lead Period under the
     provisions of Section 7.2 above, or (iii) for which NOVARTIS has exercised
     or will exercise its Development Election before the end of the applicable
     Lead Period under the provisions of Section 7.4 below.

7.4  NOVARTIS RIGHTS TO LICENSE BACK-UP COMPOUNDS. Anytime prior to the expiry
     of the Lead Period with respect a particular Drug Product Candidate,
     NOVARTIS may also, by paying in each case the Back-up Election Fee provided
     under Section 6.1 of the this Agreement, exercise its Development Election
     with respect to any one or more Back-up Compounds associated with that Drug
     Product Candidate, provided that Drug Product Candidate, or a Back-up
     Compound selected pursuant to the provisions of Section 7.2 above, is still
     in active development. Any such Back-up Compound for which NOVARTIS has
     exercised its Development Election under Section 7.4 shall become a "Drug
     Product Candidate Back-up Candidate" subject to the terms and conditions of
     this Agreement.

7.5  NOVARTIS OBLIGATIONS WITH RESPECT TO DRUG PRODUCT CANDIDATE BACK-UP
     CANDIDATES. So long as NOVARTIS is using commercially reasonable efforts,
     pursuant to the provisions of Sections 3.6 and 5.6 of this Agreement, with
     respect to the development of a particular Drug Product Candidate or the
     commercialization of a particular Drug Product, NOVARTIS shall have no
     obligation to develop any of the Drug Product Candidate Back-up Candidates
     associated with that Drug Product Candidate or Drug Product. As soon as
     NOVARTIS ceases the development of a particular Drug Product Candidate,
     NOVARTIS' obligations to use diligent, commercially reasonable efforts will
     immediately shift from the discontinued Drug Product Candidate to an
     associated Drug Product Candidate Back-up Compound. If NOVARTIS ceases the
     development of a particular Drug Product Candidate and does not commence
     development of a Drug Product Candidate Back-up Compound pursuant to the
     foregoing, the license to the Drug Product Candidate and its Back-up
     Compounds under this Agreement will expire and the license rights will
     revert to VERTEX.

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                                  ARTICLE VIII
                              INTELLECTUAL PROPERTY

     8.1.      PATENTABLE INVENTIONS AND KNOW-HOW.

               8.1.1.  Ownership. Any inventions made and all Know-How generated
                       by either party or its Affiliates during the term of this
                       Agreement, and Controlled by such party, relating to the
                       manufacture or use of Bulk Drug Substance, a Drug Product
                       Candidate or a Drug Product, or a prodrug thereof, will
                       be disclosed to the other party promptly after the
                       disclosing party recognizes the significance thereof. All
                       patents and technology shall be owned by the party making
                       the invention claimed or contained therein or, if such
                       invention is made jointly, shall be owned jointly, all as
                       determined in accordance with U.S. laws of inventorship.

               8.1.2.  Patent Prosecution. VERTEX shall be responsible for the
                       preparation, filing, prosecution and maintenance of all
                       patents and patent applications included in VERTEX
                       Patents and all patents and patent applications included
                       in Patents claiming inventions jointly owned with
                       NOVARTIS. NOVARTIS shall be responsible for the
                       preparation, filing, prosecution and maintenance of all
                       patents and patent applications included in NOVARTIS
                       Patents. In each case the responsible party shall consult
                       from time to time with the other party with respect
                       thereto. VERTEX shall provide NOVARTIS with periodic
                       reports listing the jurisdictions in which the VERTEX
                       Patents licensed hereunder have been filed. Subject to
                       the next succeeding sentences, VERTEX will file patent
                       applications with respect to those VERTEX Patents in such
                       other countries as NOVARTIS shall request in writing, all
                       such other countries being countries in which NOVARTIS
                       would customarily file its own cases dealing with similar
                       subject matters. The party initially responsible for
                       preparation, filing, prosecution and maintenance of a
                       particular Patent (the "Initial Responsible Party") shall
                       give thirty (30) days advance notice (the "Discontinuance
                       Election") to the other party of any decision to cease
                       preparation, filing, prosecution and maintenance of that
                       Patent in any jurisdiction (a "Discontinued Patent"). In
                       such case, the other party may elect at its sole
                       discretion to continue preparation, filing and
                       prosecution or maintenance of the Discontinued Patent at
                       its sole expense. The party so continuing shall own any
                       such Patent; and the Initial Responsible Party shall
                       execute such documents and perform such acts as may be
                       reasonably necessary for the other party to file or to
                       continue prosecution or maintenance, including assigning
                       ownership of such Patent to such electing party.
                       Discontinuance may be on a country-by-country basis or
                       for a patent application or patent series in total.

               Each party will consult the other party with respect to its
choice of patent counsel and will keep that party continuously informed of all
matters relating to the preparation, filing, prosecution and maintenance of
Patents covered by this Agreement. Each party shall endeavor

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in good faith to coordinate its efforts with those of the other party to
minimize or avoid interference with the prosecution of the other party's patent
applications.

               8.1.3.   Costs.  Costs incurred in the  preparation,  prosecution
and maintenance of Patents shall be borne by each party as set forth in Section
8.3 of the Research Agreement.

     8.2.      Infringement Claims by Third Parties.

               8.2.1.  Notice. If the manufacture, use or sale of Bulk Drug
                       Substance and/or Drug Product results in a claim against
                       a party hereto for patent infringement or for inducing or
                       contributing to patent infringement ("Infringement
                       Claim"), the party first having notice of an Infringement
                       Claim shall promptly notify the other in writing. The
                       notice shall set forth the facts of the Infringement
                       Claim in reasonable detail.

               8.2.2.  Third Party Licenses. In the event that practicing the
                       Technology in connection with the manufacture, use or
                       sale of a Drug Product in any country would infringe a
                       Third Party's patent, then VERTEX will use reasonable
                       efforts to obtain a license under the Third Party's
                       patents with a right to sublicense to NOVARTIS, under
                       terms reasonably acceptable to both VERTEX and NOVARTIS,
                       [***]

               8.2.3.  Discontinued Sales, License or Defense of Suit. If the
required license is either unavailable or its terms are unacceptable both to
VERTEX and to NOVARTIS, then NOVARTIS may elect in its sole discretion to
discontinue sales of the Drug Product in such country or to undertake the
defense of a patent infringement action or the prosecution of a declaratory
judgment action with respect to the Third Party patents. [***] Provided that
NOVARTIS is conducting the defense of the Infringement Claim or the prosecution
of such declaratory judgment actions, [***]. The costs and expenses of all suits
brought by a party under this Section 8.2.3 shall be reimbursed to such party
and then to the other party, if it participates in such suit, PRO RATA, out of
any damages or other monetary awards recovered therein in favor of VERTEX or
NOVARTIS. [***] No settlement or consent judgment or other voluntary final
disposition of a suit under this Section 8.2 may be entered into without the
joint consent of VERTEX and NOVARTIS (which consent shall not be unreasonably
withheld).

     8.3.      Infringement Claims Against Third Parties.

               8.3.1.  VERTEX and NOVARTIS each agree to take reasonable actions
                       to protect their respective patents and technology from
                       infringement and from unauthorized possession or use.

               8.3.2.  If any VERTEX Patents or NOVARTIS Patents are infringed
or VERTEX Know-How or NOVARTIS Know-How is misappropriated, as the case may be,
by a Third Party, the party to this Agreement first having knowledge of such
infringement or misappropriation, or knowledge of a reasonable probability of
such infringement or misappropriation, shall promptly notify the other in
writing. The notice shall set forth the facts of such infringement or
misappropriation in reasonable detail. The owner of the patent or technology, or
VERTEX, in the case of joint ownership between the parties hereto, shall have
the primary right, but not the obligation, to institute, prosecute, and control
with its own counsel any action or proceeding with respect to infringement or
misappropriation of such patent or technology and the other party shall have the
right, at its own expense, to be represented in such action by its own counsel.
If the

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party having the primary right or responsibility to institute, prosecute, and
control such action or prosecution fails to do so within a period of one hundred
twenty (120) days after receiving notice of the infringement, the other party
shall have the right to bring and control any such action by counsel of its own
choice, and the other shall have the right, at its own expense, to be
represented in any such action by counsel of its own choice. If one party brings
any such action or proceeding, the second party may be joined as a party
plaintiff and, in case of joining, the second party agrees to give the first
party reasonable assistance and authority to file and to prosecute such suit.
The costs and expenses of all suits brought by a party under this Section 8.3.2
shall be reimbursed to such party and to the other party, if it participates in
such suit, PRO RATA, out of any damages or other monetary awards recovered
therein in favor of VERTEX or NOVARTIS. [***] No settlement or consent judgment
or other voluntary final disposition of a suit under this Section 8.3 may be
entered into without the joint consent of VERTEX and NOVARTIS (which consent
shall not be unreasonably withheld).

     8.4.      NOTICE OF CERTIFICATION. VERTEX and NOVARTIS each shall
immediately give notice to the other of any certification filed under the U.S.
"Drug Price Competition and Patent Term Restoration Act of 1984" claiming that a
VERTEX Patent or a NOVARTIS Patent is invalid or that any infringement will not
arise from the manufacture, use or sale of any product by a third party. If
VERTEX decides not to bring infringement proceedings against the entity making
such a certification, VERTEX shall give notice to NOVARTIS of its decision not
to bring suit within twenty-one (21) days after receipt of notice of such
certification. NOVARTIS may then, but is not required to, bring suit against the
party that filed the certification. Any suit by NOVARTIS or VERTEX shall either
be in the name of NOVARTIS or in the name of VERTEX, or jointly by NOVARTIS and
VERTEX, as may be required by law. For this purpose, the party not bringing suit
shall execute such legal papers necessary for the prosecution of such suit as
may be reasonably requested by the party bringing suit.

     8.5.      PATENT TERM EXTENSIONS. The parties shall cooperate in good faith
with each other in gaining patent term extension wherever applicable to VERTEX
Patents and NOVARTIS Patents covering Drug Product Candidates or Drug Products.
NOVARTIS and VERTEX shall mutually determine which patents shall be extended.
All filings for such extension shall be made by the party who owns the patent,
provided, however, that in the event that the party who owns the patent elects
not to file for an extension, such party shall (i) inform the other party of its
intention not to file and (ii) grant the other party the right to file for such
extension.

                                   ARTICLE IX
                         REPRESENTATIONS AND WARRANTIES

     9.1.      REPRESENTATIONS AND WARRANTIES OF VERTEX.  VERTEX represents and
warrants to NOVARTIS as follows:

               9.1.1.  AUTHORIZATION. This Agreement has been duly executed and
                       delivered by VERTEX and constitutes the valid and binding
                       obligation of VERTEX, enforceable against VERTEX in
                       accordance with its terms except as enforceability may be
                       limited by bankruptcy, fraudulent conveyance, insolvency,
                       reorganization, moratorium and other laws relating to or
                       affecting creditors' rights generally and by general
                       equitable principles.

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                       The execution, delivery and performance of this Agreement
                       have been duly authorized by all necessary action on the
                       part of VERTEX, its officers and directors.

               9.1.2.  NO THIRD PARTY RIGHTS. Except as previously disclosed in
                       writing to NOVARTIS on or before the date set forth on
                       the first page hereof, (a) VERTEX owns or possesses
                       adequate licenses or other rights to use all VERTEX
                       Technology, and to grant the licenses herein; and (b) the
                       granting of the licenses to NOVARTIS hereunder does not
                       violate any right known to VERTEX of any Third Party.

               9.1.3.  NO THIRD PARTY PATENTS. Except as disclosed in writing by
                       VERTEX to NOVARTIS or its agents, to VERTEX's knowledge
                       and based on its current understanding of the Drug
                       Product Candidate(s) and its use, the development,
                       manufacture, use or sale of any Bulk Drug Substance, Drug
                       Product Candidates or Drug Products pursuant to this
                       Agreement will not infringe or conflict with any Third
                       Party right or patent, and VERTEX is not aware of any
                       issued patent or pending patent application that, if
                       issued, would be infringed by the development,
                       manufacture, use or sale of any Bulk Drug Substance, Drug
                       Product Candidates or Drug Products pursuant to this
                       Agreement.

               9.1.4.  MAINTENANCE OF PATENTS AND LICENSES. Subject to the
                       provisions of Section 8.1.2 with respect to Discontinued
                       Patents, VERTEX will take all reasonable steps to obtain
                       any consent required for and to maintain in effect,
                       including by means of extension, any license, sublicense,
                       patent or patent application applicable to the Field for
                       which it has granted rights to NOVARTIS hereunder.

     9.2.     REPRESENTATIONS AND WARRANTIES OF NOVARTIS.  NOVARTIS represents
and warrants to VERTEX as follows:

               9.2.1.  AUTHORIZATION. This Agreement has been duly executed and
                       delivered by NOVARTIS and constitutes the valid and
                       binding obligation of NOVARTIS, enforceable against
                       NOVARTIS in accordance with its terms, except as
                       enforceability may be limited by bankruptcy, fraudulent
                       conveyance, insolvency, reorganization, moratorium and
                       other laws relating to creditors' rights generally and by
                       general equitable principles. The execution, delivery and
                       performance of this Agreement have been duly authorized
                       by all necessary action on the part of NOVARTIS, its
                       officers and directors.

               9.2.2.  NO THIRD PARTY RIGHTS. Except as previously disclosed in
                       writing to VERTEX on or before the date set forth on the
                       first page hereof, (a) NOVARTIS owns or possesses
                       adequate licenses or other rights to use all NOVARTIS
                       Technology, and to grant the licenses herein; and (b) the
                       granting of the licenses to VERTEX hereunder does not
                       violate any right known to NOVARTIS of any Third Party.

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               9.2.3.  NO THIRD PARTY PATENTS. Except as disclosed in writing by
                       NOVARTIS to VERTEX or its agents, to NOVARTIS' knowledge
                       and based on its current understanding of the Drug
                       Product Candidate(s) and its use, the manufacture, use or
                       sale of any Bulk Drug Substance, Drug Product Candidates
                       or Drug Products pursuant to this Agreement will not
                       infringe or conflict with any Third Party right or
                       patent, and NOVARTIS is not aware of any issued patent or
                       pending patent application that, if issued, would be
                       infringed by the development, manufacture, use or sale of
                       any Bulk Drug Substance, Drug Product Candidates or Drug
                       Products pursuant to this Agreement.

               9.2.4.  MAINTENANCE OF PATENTS AND LICENSES. Subject to the
                       provisions of Section 8.1.2 with respect to Discontinued
                       Patents, NOVARTIS will take all reasonable steps to
                       obtain any consent required for and to maintain in
                       effect, including by means of extension, any license,
                       sublicense, patent or patent application applicable to
                       the Field for which it has granted rights to VERTEX
                       hereunder.

                                    ARTICLE X
                                 CONFIDENTIALITY

     10.1.     UNDERTAKING. During the term of this Agreement, each party shall
keep confidential, and other than as provided herein shall not use or disclose,
directly or indirectly, any trade secrets, confidential or proprietary
information, or any other knowledge, information, documents or materials, owned,
developed or possessed by the other party, whether in tangible or intangible
form, the confidentiality of which such other party takes reasonable measures to
protect, including but not limited to VERTEX Technology and NOVARTIS Technology.

               10.1.1. Each party shall take any and all lawful measures to
                       prevent the unauthorized use and disclosure of such
                       information, and to prevent unauthorized persons or
                       entities from obtaining or using such information.

               10.1.2. Each party further agrees to refrain from directly or
                       indirectly taking any action which would constitute or
                       facilitate the unauthorized use or disclosure of such
                       information. Each party may disclose such information to
                       its officers, employees and agents, to authorized
                       licensees and sublicensees, and to subcontractors in
                       connection with the development or manufacture of Bulk
                       Drug Substance, Drug Product Candidates or Drug Products,
                       to the extent necessary to enable such parties to perform
                       their obligations hereunder or under the applicable
                       license, sublicense or subcontract, as the case may be;
                       provided, that such officers, employees, agents,
                       licensees, sublicensees and subcontractors have entered
                       into appropriate confidentiality agreements for secrecy
                       and non-use of such information which by their terms
                       shall be enforceable by injunctive relief at the instance
                       of the disclosing party.

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               10.1.3. Each party shall be liable for any unauthorized use and
                       disclosure of such information by its officers, employees
                       and agents and any such sublicensees and subcontractors.

     10.2.     EXCEPTIONS.  Notwithstanding the foregoing, the provisions
of Section 10.1 hereof shall not apply to knowledge, information, documents or
materials which the receiving party can conclusively establish:

               10.2.1. have entered the public domain without such party's
                       breach of any obligation owed to the disclosing party;

               10.2.2. are permitted to be disclosed by the prior written
                       consent of the disclosing party;

               10.2.3. have become known to the receiving party from a source
                       other than the disclosing party, other than by breach of
                       an obligation of confidentiality owed to the disclosing
                       party;

               10.2.4. are disclosed by the disclosing party to a Third Party
                       without restrictions on its disclosure;

               10.2.5. are independently developed by the receiving party
                       without breach of this Agreement; or

               10.2.6. are required to be disclosed by the receiving party to
                       comply with applicable laws or regulations, to defend or
                       prosecute litigation or to comply with governmental
                       regulations, provided that the receiving party provides
                       prior written notice of such disclosure to the disclosing
                       party and takes reasonable and lawful actions to avoid or
                       minimize the degree of such disclosure.

     10.3.     PUBLICITY.  The  parties  will agree  upon the  timing and
content of any initial press release or other public communications relating to
this Agreement and the transactions contemplated herein.

               10.3.1. Except to the extent already disclosed in that initial
                       press release or other public communication, no public
                       announcement concerning the existence or the terms of
                       this Agreement or concerning the transactions described
                       herein shall be made, either directly or indirectly, by
                       VERTEX or NOVARTIS, except as may be legally required by
                       applicable laws, regulations, or judicial order, without
                       first obtaining the approval of the other party and
                       agreement upon the nature, text, and timing of such
                       announcement, which approval and agreement shall not be
                       unreasonably withheld.

               10.3.2. The party desiring to make any such public announcement
shall provide the other party with a written copy of the proposed announcement
in sufficient time prior to public release to allow such other party to comment
upon such announcement, prior to public release.

     10.4.     SURVIVAL.  The  provisions of this Article X shall survive the
termination of this Agreement and shall extend for a period of five (5) years
thereafter.

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                                   ARTICLE XI
                                   PUBLICATION

     NOVARTIS reserves the sole right to publish or publicly present the results
of the Development Program and information concerning Drug Product Candidates
and Back-up Compounds (collectively, the "Results"), subject to the following
terms and conditions. NOVARTIS will submit a draft of any proposed manuscript or
speech to VERTEX for comments at least thirty (30) days prior to submission for
publication or oral presentation. VERTEX shall notify NOVARTIS in writing within
fifteen (15) days of receipt of such draft whether such draft contains (i)
information of VERTEX which it considers to be confidential under the provisions
of Article IX hereof, or (ii) information that if published would have an
adverse effect on a patent application covering the subject matter of this
Agreement which VERTEX intends to file,. In any such notification, VERTEX shall
indicate with specificity its suggestions regarding the manner and degree to
which NOVARTIS may disclose such information. In the case of item (ii) above,
VERTEX may request a delay and NOVARTIS shall delay such publication, for a
period not exceeding ninety (90) days, to permit the timely preparation and
filing of a patent application or an application for a certificate of invention
on the information involved. In the case of item (i) above, NOVARTIS may not
publish confidential information of VERTEX without its consent in violation of
Article IX of this Agreement. The parties agree that authorship of any
publication will be determined based on the customary standards then being
applied in the relevant scientific journal.

     This Article XI shall terminate with the termination of this Agreement, but
the provisions of Article X hereof shall continue to govern the disclosure by
one party, whether by publication or otherwise, of Confidential Information of
the other, during the period set forth in Section 10.4.

                                   ARTICLE XII
                               DISPUTE RESOLUTION

     12.1.     GOVERNING  LAW, AND  JURISDICTION.  This  Agreement shall be
governed and construed in accordance with the internal laws of the State of New
York.

     12.2.     DISPUTE RESOLUTION PROCESS. Except as otherwise explicitly
provided herein, in the event of any controversy or claim arising out of or
relating to any provision of this Agreement, or the collaborative effort
contemplated hereby, the parties shall, and either party may, initially refer
such dispute to the Joint Steering Committee, and failing resolution of the
controversy or claim within thirty (30) days after such referral, the matter
shall be referred to the Chief Executive Officer of VERTEX and the Chief
Executive Officer of NOVARTIS who shall, as soon as practicable, attempt in good
faith to resolve the controversy or claim. If such controversy or claim is not
resolved within sixty (60) days of the date of initial referral of the matter to
the JSC, either party shall be free to initiate proceedings in any court having
requisite jurisdiction.

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                                  ARTICLE XIII

                              TERM AND TERMINATION

     13.1.     TERM. The term of this Agreement shall extend with respect to a
Drug Product in a particular country until the later of: (a) the last to expire
of any VERTEX Patents containing a Valid Patent Claim covering the Drug Product
or its use or manufacture in that country; or (b) if there is no such Valid
Patent Claim under a VERTEX Patent in a particular country, ten (10) years from
the earlier of the date Regulatory Approval is received in that country for sale
of the Drug Product, or the date of First Commercial Sale of the Drug Product in
that country.

     13.2.     TERMINATION FOR CAUSE. In addition to rights of termination which
may be granted to either party under other provisions of this Agreement, either
party may terminate this Agreement upon sixty (60) days prior written notice to
the other party upon the material breach by such other party of any of its
obligations under this Agreement, provided that such termination shall become
effective only if the breaching party shall fail to remedy or cure the breach
within such sixty (60) day period.

     13.3.     TERMINATION FOR BANKRUPTCY. If at any time during the term of
this Agreement, an Event of Bankruptcy (as defined below) relating to either
party (the "Bankrupt Party") occurs, the other party (the "Other Party") shall
have, in addition to all other legal and equitable rights and remedies available
hereunder, the option to terminate this Agreement upon 30 days' written notice
to the Bankrupt Party. It is agreed and understood that if the Other Party does
not elect to terminate this Agreement upon the occurrence of an Event of
Bankruptcy, except as may otherwise be agreed with the trustee or receiver
appointed to manage the affairs of the Bankrupt Party, the Other Party shall
continue to make all payments required of it under this Agreement as if the
Event of Bankruptcy had not occurred, and the Bankrupt Party shall not have the
right to terminate any license granted herein. As used above, the term "Event of
Bankruptcy" shall mean (a) dissolution, termination of existence, liquidation or
business failure of either party; (b) the appointment of a custodian or receiver
for either party who has not been terminated or dismissed within 90 days; (c)
the institution by either party of any proceeding under national, federal or
state bankruptcy, reorganization, receivership or other similar laws affecting
the rights of creditors generally or the making by either party of a composition
or any assignment or trust mortgage for the benefit of creditors or under any
national, federal or state bankruptcy, reorganization, receivership or other
similar law affecting the rights of creditors generally, which proceeding is not
dismissed within 90 days of filing.

     13.4.     TERMINATION BY NOVARTIS.  [***]

     13.5.     EFFECT OF TERMINATION.

                  (a) Termination of this Agreement for any reason, or
expiration of this Agreement, will not affect: (i) obligations, including the
payment of any royalties and any supply price payments, which have accrued as of
the date of termination or expiration, and (ii) rights and obligations which,
from the context thereof, are intended to survive termination or expiration of
this Agreement.

                  (b) For each country, at the end of the Agreement term as
provided in Section 13.1 hereof in respect of a Drug Product, NOVARTIS shall
have a perpetual, nonexclusive, transferable, paid-up, royalty-free license
under VERTEX Technology, in each case which is in

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existence at the end of such Agreement term, to use, make, have made and sell
that Drug Product in that country and to make or have made Drug Product for use
and sale in that country.

                                   ARTICLE XIV
                                 INDEMNIFICATION

     14.1.     INDEMNIFICATION BY VERTEX. VERTEX will indemnify and hold
NOVARTIS and its Affiliates, and their employees, officers and directors
harmless against any loss, damages, action, suit, claim, demand, liability,
expense, bodily injury, death or property damage (a "Loss"), that may be
brought, instituted or arise against or be incurred by such persons to the
extent such Loss is based on or arises out of:

               14.1.1. the development, manufacture, use, storage or handling of
                       a Drug Product Candidate or a Drug Product by VERTEX or
                       its Affiliates or their representatives, agents or
                       subcontractors under this Agreement, or any actual or
                       alleged violation of law resulting therefrom (with the
                       exception of Losses based on infringement or
                       misappropriation of intellectual property rights); or

               14.1.2. the breach by VERTEX of any of its covenants,
                       representations or warranties set forth in this
                       Agreement; and

               14.1.3. provided however, that the foregoing indemnification
shall not apply to any Loss to the extent such Loss is caused by the negligent
or willful misconduct of NOVARTIS or its Affiliates.

     14.2.     INDEMNIFICATION BY NOVARTIS. NOVARTIS will indemnify and hold
VERTEX, and its Affiliates, and their employees, officers and directors harmless
against any Loss that may be brought, instituted or arise against or be incurred
by such persons to the extent such Loss is based on or arises out of:

               14.2.1. the development, manufacture, use, sale, storage or
                       handling of a Drug Product Candidate or a Drug Product by
                       NOVARTIS or its Affiliates or their representatives,
                       agents or subcontractors under this Agreement, or any
                       actual or alleged violation of law resulting therefrom
                       (with the exception of Losses based on infringement or
                       misappropriation of intellectual property rights); or

               14.2.2. the breach by NOVARTIS of any of its covenants,
                       representations or warranties set forth in this
                       Agreement; and

               14.2.3. provided that the foregoing indemnification shall not
apply to any Loss to the extent such Loss is caused by the negligent or willful
misconduct of VERTEX or its Affiliates.

     14.3.     CLAIMS PROCEDURES. Each Party entitled to be indemnified by the
other Party (an "Indemnified Party") pursuant to Section 14.1 or 14.2 hereof
shall give notice to the other Party (an "Indemnifying Party") promptly after
such Indemnified Party has actual knowledge of any threatened or asserted claim
as to which indemnity may be sought, and shall permit the Indemnifying Party to
assume the defense of any such claim or any litigation resulting therefrom;

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provided: That counsel for the Indemnifying Party, who shall conduct the defense
of such claim or any litigation resulting therefrom, shall be approved by the
Indemnified Party (whose approval shall not unreasonably be withheld) and the
Indemnified Party may participate in such defense at such party's expense
(unless (i) the employment of counsel by such Indemnified Party has been
authorized by the Indemnifying Party; or (ii) the Indemnified Party shall have
reasonably concluded that there may be a conflict of interest between the
Indemnifying Party and the Indemnified Party in the defense of such action, in
each of which cases the Indemnifying Party shall pay the reasonable fees and
expenses of one law firm serving as counsel for the Indemnified Party, which law
firm shall be subject to approval, not to be unreasonably withheld, by the
Indemnifying Party); and

               14.3.1. The failure of any Indemnified Party to give notice as
                       provided herein shall not relieve the Indemnifying Party
                       of its obligations under this Agreement to the extent
                       that the failure to give notice did not result in harm to
                       the Indemnifying Party.

               14.3.2. No Indemnifying Party, in the defense of any such claim
                       or litigation, shall, except with the approval of each
                       Indemnified Party which approval shall not be
                       unreasonably withheld, consent to entry of any judgment
                       or enter into any settlement which (i) would result in
                       injunctive or other relief being imposed against the
                       Indemnified Party; or (ii) does not include as an
                       unconditional term thereof the giving by the claimant or
                       plaintiff to such Indemnified Party of a release from all
                       liability in respect to such claim or litigation.

               14.3.3. Each Indemnified Party shall furnish such information
regarding itself or the claim in question as an Indemnifying Party may
reasonably request in writing and shall be reasonably required in connection
with the defense of such claim and litigation resulting therefrom.

     14.4.     COMPLIANCE. The parties shall comply fully with all applicable
laws and regulations in connection with their respective activities under this
Agreement.

     14.5.     INSURANCE. Each party shall use all commercially reasonable
efforts to maintain insurance, including product liability insurance, with
respect to its activities hereunder.

               14.5.1. Such insurance shall be in such amounts and subject to
                       such deductibles as the parties may agree based upon
                       standards prevailing in the industry at the time.

               14.5.2. Either party may satisfy its obligations under this
                       Section through self-insurance to the same extent.

               14.5.3. At such time as a Drug Product is being manufactured by a
party for commercial sale, that party shall name the other party as an
additional insured on any such policies.

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                                   ARTICLE XV
                            MISCELLANEOUS PROVISIONS

     15.1.     NOTICE OF PHARMACEUTICAL SIDE-EFFECTS. During the term of this
Agreement, each of the parties will notify appropriate authorities in accordance
with applicable law, and the other party, promptly after receipt of information
with respect to any serious adverse event (as defined by the ICH Harmonized
Tripartite Guideline on Clinical Safety Data Management), directly or indirectly
attributable to the use or application of a Development Candidate, Bulk Drug
Substance, a Drug Product Candidate or a Drug Product.

     15.2.     WAIVER. No provision of the Agreement may be waived except in
writing by both parties hereto. No failure or delay by either party hereto in
exercising any right or remedy hereunder or under applicable law will operate as
a waiver thereof, or a waiver of a particular right or waiver of any right or
remedy on any subsequent occasion.

     15.3.     FORCE MAJEURE. Neither party shall be held liable or responsible
to the other party nor be deemed to have defaulted under or breached this
Agreement for failure or delay in fulfilling or performing any term of this
Agreement, other than an obligation to make a payment, when such failure or
delay is caused by or results from fire, floods, embargoes, government
regulations, prohibitions or interventions, war, acts of war (whether war be
declared or not), insurrections, riots, civil commotions, strikes, lockouts,
acts of God, or any other cause beyond the reasonable control of the affected
party.

     15.4.     REGISTRATION OF LICENSE. NOVARTIS may, at its expense, register
the license granted under this Agreement in any country where the use, sale or
manufacture of a Drug Product in such country would be covered by a Valid Patent
Claim. Upon request by NOVARTIS, VERTEX agrees promptly to execute any "short
form" licenses submitted to it by NOVARTIS in order to effect the foregoing
registration in such country, but such licenses shall in no way alter or affect
the obligations of the parties hereunder.

     15.5.     SEVERABILITY. It is the intention of the parties to comply with
all applicable laws domestic or foreign in connection with the performance of
its obligations hereunder. In the event that any provision of this Agreement, or
any part hereof, is found invalid or unenforceable, the remainder of this
Agreement will be binding on the parties hereto, and will be construed as if the
invalid or unenforceable provision or part thereof had been deleted, and the
Agreement shall be deemed modified to the extent necessary to render the
surviving provisions enforceable to the fullest extent permitted by law.

     15.6.     GOVERNMENT ACTS. In the event that any act, regulation,
directive, or law of a government, including its departments, agencies or
courts, should make impossible or prohibit, restrain, modify or limit any
material act or obligation of NOVARTIS or VERTEX under this Agreement, the
party, if any, not so affected shall have the right, at its option, to suspend
or terminate this Agreement as to such country, if good faith negotiations
between the parties to make such modifications to this Agreement as may be
necessary to fairly address the impact thereof, are not successful after a
reasonable period of time in producing mutually acceptable modifications to this
Agreement.

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     15.7.     GOVERNMENT APPROVALS. NOVARTIS will use reasonable efforts to
obtain any government approval required to enable this Agreement to become
effective, or to enable any payment hereunder to be made, or any other
obligation hereunder to be observed or performed. Each party will keep the other
informed of progress in obtaining any such approvals.

     15.8.     ASSIGNMENT. This Agreement may not be assigned or otherwise
transferred by either party without the prior written consent of the other
party; provided, however, that either party may assign this Agreement, without
the consent of the other party, (i) to any of its Affiliates, if the assigning
party guarantees the full performance of its Affiliates' obligations hereunder,
or (ii) in connection with the transfer or sale of all or substantially all of
its assets or business or in the event of its merger or consolidation with
another company. Any purported assignment in contravention of this Section 15.8
shall, at the option of the non-assigning party, be null and void and of no
effect. No assignment shall release either party from responsibility for the
performance of any accrued obligation of such party hereunder. This Agreement
shall be binding upon and enforceable against the successor to or any permitted
assignee from either of the parties hereto.

     15.9.     AFFILIATES. Each party may perform its obligations hereunder
personally or through one or more Affiliates, although each party shall
nonetheless be solely responsible for the performance of its Affiliates. Neither
party shall permit any of its Affiliates to commit any act (including any act of
omission) which such party is prohibited hereunder from committing directly. The
use of subcontractors by either party shall not increase the financial
obligations of the other party hereunder in any respect.

     15.10.    COUNTERPARTS. This Agreement may be executed in duplicate both of
which shall be deemed to be originals, and both of which shall constitute one
and the same Agreement.

     15.11.    NO AGENCY. Nothing herein contained shall be deemed to create an
agency, joint venture, amalgamation, partnership or similar relationship between
NOVARTIS and VERTEX. Notwithstanding any of the provisions of this Agreement,
neither party shall at any time enter into, incur, or hold itself out to third
parties as having authority to enter into or incur, on behalf of the other
party, any commitment, expense, or liability whatsoever, and all contracts,
expenses and liabilities undertaken or incurred by one party in connection with
or relating to the development, manufacture or sale of Bulk Drug Substance, Drug
Product Candidates or Drug Products shall be undertaken, incurred or paid
exclusively by that party, and not as an agent or representative of the other
party.

     15.12.    NOTICE. All communications between the parties with respect to
any of the provisions of this Agreement will be sent to the addresses set out
below, or to other addresses as designated by one party to the other by notice
pursuant hereto, by prepaid certified, air mail (which shall be deemed received
by the other party on the seventh business day following deposit in the mails),
or by cable, telex, facsimile transmission, or other electronic means of
communication (which shall be deemed received when transmitted), with
confirmation by letter given by the close of business on or before the next
following business day:

 License, Development and Commercialization Agreement -- Confidential -- Page 29
<Page>

               If to NOVARTIS, at:

                     NOVARTIS PHARMA AG
                     Business Development and Licensing
                     P.O. Box
                     CH-4002
                     Basel, Switzerland
                     Attention:  Victor A. Hartmann, Vice President

                   with a copy to: Legal Services, at the address referenced
               above and

               if to VERTEX, at:
                     Vertex Pharmaceutical Incorporated
                     130 Waverly Street
                     Cambridge, MA U.S.A. 02139-4211
                     Attention:  President

               with a copy to:
                     Legal Department
                     Attention: General Counsel

     15.13.    HEADINGS. The paragraph headings are for convenience only and
will not be deemed to affect in any way the language of the provisions to which
they refer.

     15.14.    AUTHORITY. The undersigned represent that they are authorized to
sign this Agreement on behalf of the parties hereto. The parties each represent
that no provision of this Agreement will violate any other agreement that such
party may have with any other person or company. Each party has relied on that
representation in entering into this Agreement.

     15.15.    ENTIRE AGREEMENT. This Agreement, including the Schedules
appended hereto, contains the entire understanding of the parties relating to
the matters referred to herein, except as matters referenced herein are also
addressed in the Research Agreement, and may only be amended by a written
document, duly executed on behalf of the respective parties.

     15.16.    INFLATION ADJUSTMENT. All payments required to be made to VERTEX
hereunder (except any royalty payments required to be made under the provisions
of Section 6.3 hereof) shall be adjusted at the beginning of each calendar year
to reflect the impact of inflation since the date of execution of the Revised
and Restated Research Agreement, as measured by the biotech worker inflation
rate defined and reported in the Radford Survey (Radford/AON Consulting Inc.,
San Francisco, CA), or other mutually acceptable index. Notwithstanding the
foregoing, no adjustment shall be required in any calendar year in which the
appropriate inflation adjustment, if applied, would result in a change of less
than [***].

     15.17.    INVOICE REQUIREMENT. Any amounts payable to VERTEX hereunder
(except any royalty payments required to be made under the provisions of Section
6.3 hereof) shall be made within thirty days after receipt by NOVARTIS, or its
nominee designated for that purpose in advance by NOVARTIS in writing to VERTEX,
of an invoice covering such payment, which

 License, Development and Commercialization Agreement -- Confidential -- Page 30
<Page>

invoice shall conform to the extent reasonably practicable to the form of
invoice contained in Exhibit B to the Research Agreement.

     15.18.    HARDSHIP. If as a result of unforeseen events or developments
relating to the subject matter of this Agreement, the performance of this
Agreement shall cause inequitable economic hardship for one party which runs
counter to the objectives of this Agreement and which the other party cannot
reasonably and in good faith expect the first party to bear unrelieved, the
parties will meet and seek in good faith to find equitable means of amending
this Agreement to reestablish a fair and reasonable economic balance under this
Agreement between the parties hereto.

 License, Development and Commercialization Agreement -- Confidential -- Page 31
<Page>

     IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives as of the day and year first
above written.

                                VERTEX PHARMACEUTICALS INCORPORATED


                                By:
                                   ---------------------------------------------

                                       Kenneth S. Boger
                                Title: Senior Vice President and General Counsel


                                NOVARTIS PHARMA AG


                                By:
                                   ---------------------------------------------


                                Title:
                                      ------------------------------------------


                                By:
                                   ---------------------------------------------


                                Title:
                                      ------------------------------------------

 License, Development and Commercialization Agreement -- Confidential -- Page 32
<Page>

                                  SCHEDULE 1.12

                         LIST OF DRUG PRODUCT CANDIDATES



                                 To be supplied


       License, Development and Commercialization Agreement -- Confidential
<Page>

                                  SCHEDULE 1.25


                              LIST OF MAJOR MARKETS


         [***]


       License, Development and Commercialization Agreement -- Confidential
<Page>

                                  SCHEDULE 1.29

                                NOVARTIS PATENTS


      License, Development and Commercialization Agreement -- Confidential
<Page>

                                  SCHEDULE 1.44

                                 VERTEX PATENTS


       License, Development and Commercialization Agreement -- Confidential