Document:

<PAGE>
                                                                   EXHIBIT 10.10

                                 Paul A. Brooke
                            21 E. 90th Street, #14AB
                            New York, New York 10128

March 31, 2002

Jean-Pierre Sommadossi, Ph.D.
Novirio Pharmaceuticals Limited
c/o Novirio Pharmaceuticals, Inc.
125 CambridgePark Drive
Cambridge, MA 02140

Dear Jean-Pierre:

This letter is inform you that I resign effective immediately as a director of
Novirio Pharmaceuticals Limited and, as we have agreed, will terminate my
service as a consultant to the Company. Please acknowledge your receipt of this
letter and your agreement and acknowledgement that the 60,000 Ordinary Shares
which are the subject of the Stock Restriction Agreement dated as of December
15, 2000 by and between Novirio and me will become vested in full as of the
effective date of this termination of service.

Very truly yours,

/s/ Paul A. Brooke

Paul A. Brooke

Acknowledged and Agreed this 31st day of March 2002

NOVIRIO PHARMACEUTICALS LIMITED

By: /s/ Jean-Pierre Sommadossi
   ------------------------------------
   Jean-Pierre Sommadossi, Ph.D.
   Chairman and Chief Executive Officer<PAGE>
                                                                   EXHIBIT 10.11

                         NOVIRIO PHARMACEUTICALS LIMITED

                           SECOND AMENDED AND RESTATED
                             STOCKHOLDERS' AGREEMENT

                                 April 24, 2001
<PAGE>
                                TABLE OF CONTENTS

<TABLE>
<CAPTION>
                                                                            Page
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<S>                                                                         <C>
SECTION 1 DEFINITIONS; EFFECT ...........................................     1
      1.1   Definitions .................................................     1
      1.2   Effect ......................................................     8

SECTION 2 REGISTRATION RIGHTS ...........................................     8
      2.1   Requested Registration ......................................     8
      2.2   Company Registration. .......................................     11
      2.3   Expenses of Registration ....................................     12
      2.4   Registration Procedures .....................................     12
      2.5   Registration on Form S-3 ....................................     15
      2.6   Indemnification. ............................................     15
      2.7   Information by Purchaser ....................................     18
      2.8   Rule 144 Reporting ..........................................     18
      2.9   Transfer of Registration Rights .............................     19
      2.10  General .....................................................     19
      2.11  Other Registration Rights ...................................     19
      2.12  Lock-up Agreements ..........................................     19
      2.13  Mergers, Etc ................................................     20
      2.14  Termination .................................................     20

SECTION 3 AFFIRMATIVE COVENANTS OF THE COMPANY, THE PURCHASERS AND THE
STOCKHOLDERS ............................................................     20
      3.1   Board Representation and Voting Agreement. ..................     20
      3.2   Voting and Sale or Tender of Shares .........................     22
      3.3   Termination. ................................................     23

SECTION 4 PREEMPTIVE RIGHTS .............................................     23
      4.1   Right to Purchase ...........................................     23
      4.2   Price .......................................................     24
      4.3   Closing .....................................................     25
      4.4   Termination .................................................     25

SECTION 5 RESTRICTIONS ON TRANSFER; CO-SALE .............................     25
      5.1   Restrictions ................................................     25
      5.2   Right of First Refusal Applicable to Stockholders ...........     25
      5.3   Right of Co-Sale Applicable to Stockholders .................     27
      5.4   Right of First Refusal Applicable to Purchasers .............     28
      5.5   Right of Co-Sale Applicable to the Purchasers and Stockholders    29

SECTION 6 CONFIDENTIALITY ................................................    30
      6.1   Confidentiality ..............................................    30
      6.2   Enforcement ..................................................    31
</TABLE>

                                       i
<PAGE>
<TABLE>
<S>                                                                         <C>
SECTION 7 MISCELLANEOUS ..................................................    31
      7.1   Waivers and Amendments .......................................    31
      7.2   Governing Law ................................................    31
      7.3   Successors and Assigns .......................................    31
      7.4   Entire Agreement .............................................    31
      7.5   Notices ......................................................    31
      7.6   Severability .................................................    32
      7.7   Titles and Subtitles .........................................    32
      7.8   Counterparts .................................................    32
      7.9   Consent to Jurisdiction ......................................    32
      7.10  Authorization of Preferred Shares ............................    32
      7.11  Filing of this Agreement .....................................    32
      7.12  Additional Ordinary Shares; Joinder ..........................    32
      7.13  Additional Purchasers.........................................    33
      7.14  Permitted Transfers...........................................    33
</TABLE>

                                       ii
<PAGE>
                         NOVIRIO PHARMACEUTICALS LIMITED

                           SECOND AMENDED AND RESTATED
                             STOCKHOLDERS' AGREEMENT

            THIS SECOND AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT
("Agreement") is entered into as of April 24, 2001, by and among NOVIRIO
PHARMACEUTICALS LIMITED, a corporation formed under the laws of the Cayman
Islands (the "COMPANY"), the Purchasers (as defined herein) and the Stockholders
(as defined herein).

                                    RECITALS

            WHEREAS, the Company has at the date hereof authorized share capital
consisting of 123,091,257 Ordinary Shares (as defined herein), 12,413,793 Series
A Preferred Shares (as defined herein), 5,555,556 Series B Preferred Shares (as
defined herein), and 9,939,394 Series C Preferred Shares (as defined herein);
and

            WHEREAS, the Company and the holders of the outstanding Series A
Preferred Shares, the outstanding Series B Preferred Shares and the outstanding
Ordinary Shares are parties to an Amended and Restated Stockholders' Agreement
dated as of August 6, 1999 (the "PRIOR AGREEMENT");

            WHEREAS, the purchasers of the Series C Preferred Shares require
similar rights to those set forth in the Prior Agreement as a condition to their
purchase of Series C Preferred Shares;

            WHEREAS, each Stockholder and each Purchaser will, by the Closing
Date, have a substantial investment in the Company by reason of its ownership of
the securities of the Company shown on Schedule A hereto; and

            WHEREAS, the parties believe that it is in the best interests of the
Company, the Purchasers and the Stockholders to make provision for (a) the
future disposition of certain shares of the Company and (b) other matters
relating to the governance of the Company;

            NOW, THEREFORE, in consideration of the mutual promises and
covenants hereinafter set forth, the parties hereto agree to amend and restate
the Prior Agreement as follows:

                                   SECTION 1

                              DEFINITIONS; EFFECT

            1.1 Definitions. As used in this Agreement, the following terms
shall have the following respective meanings:

            "10-DAY PERIOD" shall have the meaning set forth in Section 5.4(b).
<PAGE>
                                                                               2

            "15-DAY PERIOD" shall have the meaning set forth in Section 5.2(b).

            "AFFILIATE" shall have the meaning given such term in the Purchase
Agreement.

            "AGREEMENT" shall have the meaning set forth in the first paragraph
of this Agreement.

            "BBB" shall mean BB Bioventures L.P., a Delaware limited
partnership.

            "BOARD" shall have the meaning set forth in Section 3.1(a).

            "CHARTER" shall have the meaning given such term in the Purchase
Agreement.

            "CLOSING DATE" shall have the meaning given such term in the
Purchase Agreement.

            "CO-SALE PARTICIPANT" shall have the meaning set forth in Section
5.3(a).

            "CO-SELLER" shall have the meaning set forth in Section 5.5(a).

            "COMMISSION" shall mean the United States Securities and Exchange
Commission or any other federal agency at the time administering the Securities
Act.

            "COMPANY" shall have the meaning set forth in the first paragraph of
this Agreement.

            "COMPANY REGISTRATION CUTBACK" shall have the meaning set forth in
Section 2.2(b).

            "COMPETITOR" shall mean any Person having as a principal line of
business the discovery, development and commercialization of antiviral
therapeutics.

            "CONVERTIBLE SECURITIES" shall mean securities or obligations that
are exercisable for, convertible into or exchangeable for Ordinary Shares. The
term includes options, warrants or other rights to subscribe for or purchase
Ordinary Shares or to subscribe for or purchase other securities that are
convertible into or exchangeable for Ordinary Shares.

            "CURRENT MARKET PRICE" per share shall mean, as of the date of
determination, (a) the median of the daily Market Price under clause (a) or (b)
of the definition thereof of the common stock (or other security) of the
applicable Person during the immediately preceding thirty (30) trading days
ending on such date, and (b) if such security is not then listed or admitted to
trading on any national securities exchange or quoted in the over-the-counter
market, then the Market Price under clause (c) of the definition thereof on such
date.
<PAGE>
                                                                               3

            "DEMAND REGISTRATION CUTBACK" shall have the meaning set forth in
Section 2.1(b).

            "EQUITY INCENTIVE PLAN" shall have the meaning given such term in
the Purchase Agreement.

            "EXCLUDED SECURITIES" means (i) securities offered to the public
pursuant to a registration statement filed under the Securities Act in
connection with a Qualified IPO; (ii) securities issued pursuant to the
acquisition of another Person by the Company by merger, consolidation,
amalgamation, exchange of shares, the purchase of substantially all of the
assets or otherwise which has been approved by the Supermajority Purchasers;
(iii) Convertible Securities or Ordinary Shares issued to any employees,
officers, directors, consultants or advisors of the Company or a Subsidiary
pursuant to the Equity Incentive Plan; (iv) securities issued to the Company's
members in connection with any share split, share dividend, recapitalization,
split-up, subdivision or other similar event; (v) Purchased Securities; (vi)
Ordinary Shares issued to the Purchasers upon the conversion or exercise of the
Purchased Securities; (vii) Ordinary Shares issued pursuant to the exercise of
Convertible Securities or other awards granted under the Equity Incentive Plan;
and (viii) such number of Ordinary Shares, not to exceed 10,000, issuable upon
authorization of Jean-Pierre Sommadossi pursuant to the resolution of the
Company's Board of Directors dated June 15, 1999 which have not been issued as
of the date hereof or which are subsequently forfeited by a person to whom such
Ordinary Shares have been issued

            "FAMILY MEMBER" shall mean, as to any Person, such Person's spouse,
child (including a stepchild or an adopted child), grandchildren and a trust for
the exclusive benefit of any one or more of them and a corporation controlled at
all times by such Person and beneficially owned by such Person and any one or
more of them.

            "FOUNDERS" shall mean Doctors Jean-Pierre Sommadossi, Raymond F.
Schinazi and Jean-Louis Imbach and a "Founder" shall mean any one of them.

            "FOUNDERS' DIRECTOR" shall have the meaning set forth in Section
3.1(a).

            "INDEMNIFIED PARTY" shall have the meaning set forth in Section
2.6(c).

            "INDEMNIFYING PARTY" shall have the meaning set forth in Section
2.6(c).

            "INDEPENDENT THIRD PARTY" shall mean any Person which immediately
prior to the contemplated transaction neither owns, nor is an Affiliate of any
Person which owns, in excess of 5% of the Ordinary Shares (calculated on an as
converted basis) outstanding at such time.

            "INITIATING PURCHASERS" shall have the meaning set forth in Section
2.1(a).

            "LIQUIDITY NOTICE" shall have the meaning set forth in Section
3.1(a).
<PAGE>
                                                                               4

            "MARKET PRICE" shall mean, as of the date of determination, (a) if
the common stock (or other security) of the applicable Person is listed on a
national securities exchange, the closing price per share of such security on
such date published in The Wall Street Journal (National Edition) or, if no such
closing price on such date is published in The Wall Street Journal (National
Edition), the average of the closing bid and asked prices on such date, as
officially reported on the principal national securities exchange on which such
security is then listed or admitted to trading; or (b) if such security is not
then listed or admitted to trading on any national securities exchange but is
designated as a national market system security by the National Association of
Securities Dealers, Inc., the last trading price of such security on such date;
or (c) if neither of (a) or (b) is applicable, a market price per share of such
security determined (i) mutually by the Board of Directors and the holders of a
majority of the shares of Preferred Shares, or, (ii) if the Board of Directors
and the holders of a majority of the Preferred Shares shall fail to agree, in
the manner set forth in Article 7(6)(e) of the Company's Articles of
Association, as in effect on the date hereof.

            "NEW SHARES" shall mean (a) any Ordinary Shares or Preferred Shares
or other equity securities of the Company whether now authorized or not, (b) any
rights, options, or warrants to purchase said shares, and (c) securities of any
type whatsoever that are, or may become, convertible into, exercisable,
exchangeable, or carrying rights to subscribe for any equity securities of the
Company (collectively with the securities referred to in clause (b) above,
"Options"); provided, however, that "New Shares" does not include Excluded
Securities.

            "NOMURA" shall mean Nomura International plc.

            "NOTICE OF PROPOSED ISSUANCE" shall have the meaning set forth in
Section 4.1(a).

            "OFFER" shall have the meaning set forth in Section 5.2(a).

            "OFFERED NEW SHARES" shall have the meaning set forth in Section
4.1(a).

            "OFFERED SECURITIES" shall have the meaning set forth in Section
5.4(a).

            "OFFERED SHARES" shall have the meaning set forth in Section 5.5(a).

            "ORDINARY SHARES" means the Ordinary Shares, $.001 par value per
share, of the Company. For purposes of calculating the Stockholders' relative
holdings of the Ordinary Shares, including without limitation for purposes of
Sections 4.1(c) and 5.2(b) hereof, all Preferred Shares of the Company shall be
deemed to have been converted into Ordinary Shares.

            "ORDINARY SHARES DEEMED OUTSTANDING" shall mean, at any given time,
the number of Ordinary Shares actually then in issue at such time, plus the
number of Ordinary Shares issuable upon conversion of the Series A Preferred
Shares, the Series B Preferred Shares and the Series C Preferred Shares, plus
the number of Ordinary Shares
<PAGE>
                                                                               5

issuable upon the exercise in full of all other Convertible Securities whether
or not such other Convertible Securities are convertible into Ordinary Shares at
such time.

            "PERSON" shall mean an individual, partnership, corporation,
association, trust, joint venture, unincorporated organization and any
government, governmental department or agency or political subdivision thereof.

            "PREFERRED OFFER" shall have the meaning set forth in Section
5.4(a).

            "PREFERRED SHARES" shall mean the Series A Preferred Shares, the
Series B Preferred Shares and the Series C Preferred Shares.

            "PRIOR AGREEMENT" shall have the meaning set forth in the Recitals.

            "PRO RATA PORTION" shall have the meaning set forth in Section
5.4(b).

            "PRO RATA SHARE" shall have the meaning set forth in Section 5.2(b).

            "PROPOSED BUYER" shall have the meaning set forth in Section 5.4(a).

            "PROPOSED TRANSFEREE" shall have the meaning set forth in Section
5.2(a).

            "PROPORTIONATE SHARE" shall have the meaning set forth in Section
4.1(c).

            "PURCHASE AGREEMENT" shall mean that certain Securities Purchase
Agreement dated the date hereof among the Company and certain of the Purchasers.

            "PURCHASED SECURITIES" shall mean the Series A Preferred Shares,
Series B Preferred Shares and the Series C Preferred Shares sold by the Company
to the Purchasers on or prior to the date hereof.

            "PURCHASER SALE OF THE COMPANY" shall have the meaning set forth in
Section 3.2.

            "PURCHASERS" shall mean collectively BB BioVentures L.P., MPM Asset
Management Investors 1998 LLC, MPM BioVentures Parallel Fund, L.P., TVM Medical
Ventures GmbH & Co. K.G., KB Lux Venture Capital Fund-Biotechnology, Cloppenburg
Automobile AG, Cloppenburg Immobil AG, Peter Merz, Raymond Flammang, Nomura
International plc, Credit Suisse First Boston Equity Partners, L.P., Credit
Suisse First Boston Equity Partners (Bermuda), L.P., EMA Partners Fund 2000,
L.P., EMA Private Equity Fund 2000, L.P., Credit Suisse First Boston U.S.
Executive Advisors, L.P., Hanseatic Americas LDC, Novartis Bioventure
Fund/Novartis International AG, Biomedical Sciences Investment Fund Pte Ltd.,
Adroit Private Equity AG, Bank America Investment Corporation, and Swan Private
Equity Verwaltungs GmbH, and with respect only to their Preferred Shares and the
Ordinary Shares into which they may be converted, Jean-Pierre Sommadossi,
Raymond F. Schinazi, Bruno Lucidi, Robert Murphy, C.K. Chu and David Carder, and
any of the respective
<PAGE>
                                                                               6

transferees of any parties listed above under Section 2.9 hereof who hold
Registrable Securities.

            "QUALIFIED IPO" shall mean a fully underwritten, firm commitment
public offering pursuant to an effective registration statement under the
Securities Act or the effectiveness of such other relevant document required
pursuant to applicable foreign laws and regulations covering the offer and sale
by the Company of Ordinary Shares in which the aggregate net proceeds to the
Company (after deducting Selling Expenses) equals or exceeds $40,000,000 and in
which the price per Ordinary Share offered to the public equals or exceeds $9.90
(such price to be equitably adjusted in the event of any share dividend, share
split, combination, recapitalization or other similar event), and the listing of
such Ordinary Shares on a nationally recognized exchange in the United States or
such foreign jurisdictions as the Company and the Supermajority Purchasers may
agree; or the Nasdaq National Market.

            "QUALIFIED PRIVATE OFFERING" shall mean a Sale of the Company that
implies a valuation of the Ordinary Shares Deemed Outstanding (excluding shares
issuable upon exercise of the Series C Warrants) which equals or exceeds $9.90
per share (such price to be equitably adjusted in the event of any stock
dividend, stock split, combination, reorganization or other similar event);
provided that the consideration paid in connection therewith consists of one or
a combination of the following: (i) cash; and (ii) securities of the acquiring
corporation which may be immediately sold to the public pursuant to an effective
registration statement under the Securities Act or pursuant to an exemption
therefrom which permits sales without limitation as to volume or the manner of
sale on a nationally recognized exchange in the United States or the Nasdaq
National Market. In the event that the consideration is paid in whole or part in
securities pursuant to (ii), the value of such securities upon the closing of
such Sale of the Company shall be the Current Market Price.

            The terms "REGISTER," "REGISTERED" and "REGISTRATION" refer to a
registration in the United States effected by preparing and filing a
registration statement in compliance with the Securities Act, and the
declaration or ordering of the effectiveness of such registration statement.

            "REGISTRABLE SECURITIES" shall mean (i) the Ordinary Shares that
have been issued to any Purchaser or that are issuable pursuant to the
conversion of the Purchased Securities or the exercise of the Series C Warrants,
(ii) any Ordinary Shares issued or issuable in respect of the shares
contemplated by clause (i) above upon any share split, share dividend,
recapitalization, split-up, subdivision or other similar event, and (iii)
Ordinary Shares issued or issuable in replacement or exchange of any of the
securities issued in clauses (i) or (ii) above, provided, however, that Ordinary
Shares that are Registrable Securities shall cease to be Registrable Securities
(a) upon any sale pursuant to an effective registration statement or Rule 144
under the Securities Act or (b) upon any transfer or assignment which does not
comply with the requirements of Section 2.9 of this Agreement.
<PAGE>
                                                                               7

            "REGISTRATION EXPENSES" shall mean all expenses incurred by the
Company in complying with Sections 2.1, 2.2 and 2.5 hereof, including, without
limitation, all registration, qualification and filing fees, printing expenses,
escrow fees, fees and disbursements of counsel for the Company, reasonable fees
and disbursements of one counsel for the Purchasers, blue sky fees and expenses,
and the expense of any special audits incident to or required by any such
registration (but excluding the compensation of regular employees of the Company
which shall be paid in any event by the Company), but not including Selling
Expenses.

            "REQUEST FOR REGISTRATION" shall have the meaning set forth in
Section 2.1(a).

            "SALE OF THE COMPANY" shall mean a single transaction or a series of
transactions pursuant to which one or more Independent Third Parties acquire (i)
share capital of the Company possessing the voting power to elect a majority of
the Company's board of directors (whether by merger, consolidation or sale or
transfer of the Company's share capital, provided, however, that a Qualified IPO
in which no purchaser purchases more than ten percent (10%) of the total number
of Ordinary Shares sold and which results in an acquisition of such voting power
shall not be a Sale of the Company); or (ii) all or substantially all of the
Company's assets determined on a consolidated basis.

            "SECURITIES ACT" shall mean the United States Securities Act of
1933, as amended, or any similar federal statute and the rules and regulations
of the Commission thereunder, all as the same shall be in effect at the time.

            "SELLING EXPENSES" shall mean all underwriting fees, discounts,
selling commissions and stock transfer taxes applicable to the Registrable
Securities registered by the Purchasers.

            "SERIES A DIRECTORS" shall have the meaning set forth in Section
3.1(a).

            "SERIES A PREFERRED SHARES" shall mean the Series A Convertible
Preferred Shares, $.001 par value per share, of the Company.

            "SERIES B DIRECTOR" shall have the meaning set forth in Section
3.1(a).

            "SERIES B PREFERRED SHARES" shall mean the Series B Convertible
Preferred Shares, $.001 par value per share, of the Company.

            "SERIES C DIRECTOR" shall have the meaning set forth in Section
3.1(a).

            "SERIES C PREFERRED SHARES" shall mean the Series C Convertible
Preferred Shares, $.001 par value per share, of the Company.

            "SERIES C WARRANTS" shall mean the warrants to purchase Ordinary
Shares issued to certain of the Purchasers pursuant to the Purchase Agreement.
<PAGE>
                                                                               8

            "STOCKHOLDERS" shall mean the persons listed on Schedule A hereto as
Stockholders.

            "SUBSIDIARY" shall have the meaning given such term in the Purchase
Agreement.

            "SUPERMAJORITY PURCHASERS" shall mean the holders of 85% of the
Ordinary Shares issued or issuable upon conversion of the Preferred Shares.

            "TVM" shall mean TVM Medical Ventures GmbH & Co. KG.

            "THIRTY DAY PERIOD" shall have the meaning set forth in Section
4.1(b).

            "TRANSFER" shall mean, with respect to any security of the Company,
any transfer, sale, gift, exchange, assignment, pledge or other disposition; in
the case of a Stockholder which is not an individual, a Transfer of Ordinary
Shares or other security held by such Stockholder shall be deemed to have been
made if any equity interest in such Stockholder is directly or indirectly
transferred, sold, given, exchanged, assigned, pledged or disposed of to any
other Person.

            "TRANSFERRING PURCHASER" shall have the meaning set forth in Section
5.4(a).

            "TRANSFERRING STOCKHOLDER" shall have the meaning set forth in
Section 5.2(a).

            1.2 Effect. This Agreement shall come into effect forthwith on the
purchase by the Purchasers of the Series C Preferred Shares pursuant to the
Purchase Agreement.

                                   SECTION 2

                               REGISTRATION RIGHTS

            2.1 Requested Registration.

                        (a) Registration Upon Demand. If at any time after the
      earlier of the third anniversary of the date hereof and the consummation
      by the Company of its initial public offering of Ordinary Shares pursuant
      to a registration under the Securities Act, the Company shall receive from
      one or more Purchasers (the "INITIATING PURCHASERS") a written request
      that the Company effect the registration under the Securities Act of
      Registrable Securities held by or issuable to such Purchasers (a "REQUEST
      FOR REGISTRATION"), the Company will:

      (i)   promptly, and in any event within 15 days, give written notice of
            the proposed registration to all other Purchasers; and
<PAGE>
                                                                               9

      (ii)  use its best efforts to effect such registration of the Registrable
            Securities (including, without limitation, the execution of an
            undertaking to file post-effective amendments, appropriate
            qualification under applicable blue sky or other state securities
            laws and appropriate compliance with applicable regulations issued
            under the Securities Act and any other governmental requirements or
            regulations) as may be so requested and as would permit or
            facilitate the sale and distribution of all or such portion of such
            Registrable Securities as are specified in such request, together
            with all or such portion of the Registrable Securities of any
            Purchaser joining in such request as are specified in a written
            request received by the Company within 15 days after receipt of such
            written notice from the Company;

            Provided, however, that the Company shall not be obligated to take
any action to effect any such registration pursuant to this Section 2.1(a):

            (A)   Within ninety (90) days immediately following the effective
                  date of any registration statement on the Commission's Form
                  S-1 (or any successor form to Form S-1) pertaining to an
                  underwritten offering of securities of the Company part or all
                  of which was for its own account unless otherwise consented to
                  by the underwriter of such offering; or

            (B)   At the request of the holders of Series C Preferred Shares,
                  after the Company has effected three (3) such Requests for
                  Registration on Form S-1 (or any successor form to Form S-1)
                  at the request of the holders of Series C Preferred Shares
                  pursuant to this Section 2.1(a), such registrations have been
                  declared or ordered effective and the securities offered
                  pursuant to such registrations have been sold; or

            (C)   At the request of the holders of Series A Preferred Shares or
                  Series B Preferred Shares, after the Company has effected
                  three (3) such Requests for Registration on Form S-1 (or any
                  successor form to S-1) at the request of the holders of Series
                  A Preferred Shares or Series B Preferred Shares pursuant to
                  this Section 2.1(a), such registrations have been declared or
                  ordered effective and the securities offered pursuant to such
                  registrations have been sold; or

            (D)   Within one hundred eighty (180) days from the effective date
                  of any registration on the Commission's Form S-1 (or any
                  successor form to Form S-1) pertaining to an underwritten
                  offering of Registrable Securities held by the Purchasers
                  initiated pursuant to a Request for Registration; or

            (E)   If the minimum estimated market value of any offering of
                  Registrable Securities pursuant to this Section 2.1 is less
                  than $5,000,000; or
<PAGE>
                                                                              10

            (F)   If at the time of any Request for Registration, the Company is
                  engaged or has fixed plans to engage within 30 days of the
                  time of the Request for Registration in a registered public
                  offering or is engaged in some other activity which, in the
                  good faith determination of the Company's Board of Directors
                  would be adversely affected by the requested registration to
                  the material detriment of the Company, then the Company may at
                  its option direct that such Request for Registration be
                  delayed for a period not in excess of ninety (90) days from
                  the effective date of such offering or, in the case of such
                  other activity, until such time as the opportunity for
                  material detriment shall have ended, provided that in no event
                  shall any delay be longer than ninety (90) days from the date
                  of receipt of the Request for Registration, such right to
                  delay a Request for Registration to be exercised by the
                  Company not more than once in any two-year period.

            Subject to the foregoing clauses (A) through (F), the Company shall
file a registration statement covering the Registrable Securities so requested
to be registered as soon as practicable after receipt of the Request for
Registration.

            If as a result of a Demand Registration Cutback (as defined in
Section 2.1(b) below) the Purchasers are not allowed to include in any such
registration at least fifty percent (50%) of their Registrable Securities
requested to be registered (whether or not a Purchaser initiated such request),
then such registration shall not count as one of the Purchasers' three (3)
Requests for Registration.

            (b) Underwriting. At the request of the Initiating Purchasers, the
distribution of the Registrable Securities covered by a Request for Registration
shall be effected by means of a firm commitment underwriting. The right of any
Purchaser to registration pursuant to Section 2.1 shall be conditioned upon such
Purchaser's participation in such underwriting and the inclusion of such
Purchaser's Registrable Securities in the underwriting to the extent provided
herein.

            The Company, together with all Purchasers proposing to distribute
their securities through such underwriting, shall enter into an underwriting
agreement in customary form with the managing underwriter(s) selected for such
underwriting by the Company which underwriter(s) shall be reasonably acceptable
to the Initiating Purchasers; provided, however, that no Purchaser shall be
required to make any representations or warranties concerning the Company or its
business, properties, prospects, financial condition or related matters.
Notwithstanding any other provision of this Section 2.1, if the managing
underwriter(s) advises the Company and the Purchasers in writing that because
the number of shares requested by the Purchasers to be included in the
registration exceeds the number which can be sold in an orderly manner in such
offering within a price range acceptable to the Purchasers requesting
registration or that marketing factors require a limitation of the number of
shares to be underwritten on behalf of the Purchasers (the "DEMAND REGISTRATION
CUTBACK"), then the Company will include in such registration, to the extent of
the number and type which the Company is
<PAGE>
                                                                              11

so advised can be sold in (or during the time of) such offering without such
interference or affect on the price or sale, first, all Registrable Securities
requested to be included by the Purchasers and second, the securities proposed
to be sold by the Company for its own account. In the event a Demand
Registration Cutback results in less than all of the Registrable Securities of
the Purchasers that are requested to be included in such registration to
actually be included in such registration, then the number of Registrable
Securities that will be included in such registration shall be shared pro rata
among all of the Purchasers of Registrable Securities that were requested to be
included in such registration based on the number of shares held by each such
Purchaser.

            If any Purchaser disapproves of the terms of the underwriting, such
Person may elect to withdraw therefrom by written notice to the Company, the
managing underwriter(s) and the other Purchasers. The Registrable Securities
and/or other securities so withdrawn shall also be withdrawn from registration;
provided, however, that, if by the withdrawal of such Registrable Securities a
greater number of Registrable Securities held by the other Purchasers may be
included in such registration (up to the maximum of any limitation imposed by
the underwriters), then the Company shall offer to the Purchasers who have
included Registrable Securities in the registration the right to include
additional Registrable Securities in the same proportion used in determining the
underwriter limitation in this Section 2.1(b).

            2.2 Company Registration.

                  (a) Notice of Registration to Purchasers. If at any time or
from time to time, the Company shall determine to register any of its
securities, either for its own account or the account of a security holder or
holders, other than (i) a registration relating solely to employee benefit
plans, or (ii) a registration relating solely to a Commission Rule 145
transaction, the Company will:

      (i)   promptly give to each Purchaser written notice thereof; and

      (ii)  include in such registration (and any related qualification under
            blue sky laws or other compliance), and in any underwriting involved
            therein, all the Registrable Securities specified in a written
            request or requests, made within twenty (20) days after receipt of
            such written notice from the Company, by any Purchaser or
            Purchasers, subject to the Company Registration Cutback.

                  (b) Underwriting. If the registration of which the Company
gives notice is for a registered public offering involving an underwriting, the
Company shall so advise the Purchasers as a part of the written notice given
pursuant to Section 2.2(a)(i). In such event the right of any Purchaser to
registration pursuant to this Section 2.2 shall be conditioned upon such
Purchaser's participation in such underwriting and the inclusion of such
Purchaser's Registrable Securities in the underwriting to the extent provided
herein. All Purchasers proposing to distribute their securities through such
underwriting shall (together with the Company and the other holders distributing
their Registrable Securities through such underwriting) enter into an
underwriting
<PAGE>
                                                                              12

agreement in the form agreed to by the Company and the managing underwriter
selected for such underwriting by the Company; provided, however, that no
Purchaser shall be required to make any representations or warranties concerning
the Company or its business, properties, prospects, financial condition or
related matters. Notwithstanding any other provision of this Section 2.2, if the
managing underwriter determines that the number of shares requested to be
included in the registration exceeds the number which can be sold in an orderly
manner in such offering within a price range acceptable to the Company or that
marketing factors require a limitation of the number of shares to be
underwritten on behalf of the Company (the "COMPANY REGISTRATION CUTBACK"), then
the Company will include in such registration, to the extent of the number and
type which the Company is so advised can be sold in (or during the time of) such
offering without such effect on the price or sale, first, all securities of the
Company proposed to be sold by the Company for its own account, second, the
Registrable Securities requested by the Purchasers to be included in such
registration, and finally, any other securities of the Company requested by
other Stockholders to be included in such registration. In the event a Company
Registration Cutback results in less than all of the securities of a particular
category identified in the immediately preceding sentence that are requested to
be included in such registration to actually be included in such registration,
then the number of securities of such category that will be included in such
registration shall be shared pro rata among all of the holders of securities of
such category that were requested to be included in such registration based on
the number of shares held by each holder of securities of such category.

            2.3 Expenses of Registration. All Registration Expenses incurred in
connection with any registration pursuant to Sections 2.1, 2.2 and 2.5, other
than Selling Expenses and the fees of counsel for any selling Stockholders
(except for the reasonable fees and expenses of one counsel to the Purchasers,
which shall be paid by the Company), shall, to the extent permitted by
applicable law, be borne by the Company. All Selling Expenses relating to
Registrable Securities registered by the Purchasers shall be borne by the
Purchasers holding such Registrable Securities pro rata on the basis of the
number of shares so registered.

            2.4 Registration Procedures. In the case of each registration
effected by the Company pursuant to this Agreement, the Company will keep each
Purchaser advised in writing as to the initiation of each registration,
qualification and compliance and as to the completion thereof. The Company will:

      (a)   keep such registration, qualification or compliance effective and
            current for a period of 180 days (or such longer period as may be
            necessary to accommodate the filing of amendments or supplements
            necessary to comply with the Securities Act) or until the Purchaser
            or Purchasers have completed the distribution described in the
            registration statement relating thereto, whichever first occurs;

      (b)   furnish such number of prospectuses and other documents incident
            thereto as a Purchaser from time to time may reasonably request;
<PAGE>
                                                                              13

      (c)   use commercially reasonable efforts to register or qualify the
            securities covered by such registration statement under such other
            securities or blue sky laws of such jurisdictions as any seller
            holding at least 10% of the Registrable Securities then being
            registered reasonably requests and do any and all other acts and
            things which may be reasonably necessary or advisable to enable such
            seller to consummate the disposition in such jurisdictions of the
            Registrable Securities owned by such seller;

      (d)   in the event of any underwritten public offering, enter into and
            perform its obligations under an underwriting agreement, in usual
            and customary form, with the managing underwriter of such offering.
            Each Purchaser participating in such underwriting shall also enter
            into and perform its obligations under such an agreement; provided,
            however, that no Purchaser shall be required to make any
            representations or warranties concerning the Company or its
            business, properties, prospects, financial condition or related
            matters;

      (e)   notify each Purchaser with Registrable Securities covered by such
            registration statement, at any time when a prospectus relating
            thereto covered by such registration statement is required to be
            delivered under the Securities Act, of the happening of any event as
            a result of which the prospectus included in such registration
            statement, as then in effect, includes an untrue statement of a
            material fact or omits to state a material fact required to be
            stated therein or necessary to make the statements therein not
            misleading in the light of the circumstances then existing and of
            any Commission stop orders or other material modifications in
            connection therewith. In such case, the Company shall promptly
            prepare a supplement or amendment to such prospectus and furnish to
            each seller of Registrable Securities a reasonable number of copies
            of such supplement to or an amendment of such prospectus as may be
            necessary so that, after delivery to the purchasers of such
            Registrable Securities, such prospectus shall not contain an untrue
            statement of a material fact or omit to state any material fact
            required to be stated therein or necessary to make the statements
            therein, in light of the circumstances under which they were made,
            not misleading;

      (f)   cause all such Registrable Securities covered by such registration
            statement to be listed on each securities exchange on which the same
            class of securities issued by the Company are then listed, if the
            listing of such Registrable Securities is then permitted under the
            rules and regulations of such exchange or if applicable, as a NASDAQ
            National Market system security and, if requested by the Purchasers
            holding Registrable Securities, cause all such Registrable
            Securities, if the Company's securities are not already listed or
            traded, to be listed on any securities exchange or if applicable, as
            a NASDAQ National Market system security reasonably requested by the
            Purchasers;
<PAGE>
                                                                              14

      (g)   provide a transfer agent and registrar for all such Registrable
            Securities not later than the effective date of such registration
            statement;

      (h)   enter into such customary agreements (including underwriting
            agreements in customary form) and take all such other actions as the
            Purchasers or the underwriters, if any, reasonably request to
            expedite or facilitate the disposition of such Registrable
            Securities (including effecting a stock split or a combination of
            shares);

      (i)   make available for inspection by any Purchaser who is selling
            Registrable Securities, any underwriter participating in any
            disposition pursuant to such registration statement and any
            attorney, accountant or other agent retained by any such seller or
            underwriter, all financial and other records, pertinent corporate
            documents and properties of the Company, and cause the Company's
            officers, directors, employees and independent accountants to supply
            all information reasonably requested by any such seller,
            underwriter, attorney, accountant or agent in connection with such
            registration statement;

      (j)   otherwise use commercially reasonable efforts to comply with all
            applicable rules and regulations of the Commission, and make
            available to its security holders, as soon as reasonably
            practicable, an earnings statement covering the period of at least
            twelve months beginning with the first day of the Company's first
            full calendar quarter after the effective date of the registration
            statement, which earnings statement shall satisfy the provisions of
            Section 11(a) of the Securities Act and Rule 158 thereunder;

      (k)   permit any Purchaser which, in its reasonable judgment, might be
            deemed to be an underwriter or a controlling Person of the Company,
            to participate in the preparation of such registration or comparable
            statement and to require the insertion therein of material,
            furnished to the Company in writing, which in the reasonable
            judgment of such Purchasers and their counsel should be included;

      (l)   in the event of the issuance of any stop order suspending the
            effectiveness of a registration statement, or of any order
            suspending or preventing the use of any related prospectus or
            suspending the qualification of any Registrable Securities included
            in such registration statement for sale in any jurisdiction, the
            Company shall use commercially reasonable efforts promptly to obtain
            the withdrawal of such order;

      (m)   use commercially reasonable efforts to cause such Registrable
            Securities covered by such registration statement to be registered
            with or approved by such other governmental agencies or authorities
            as may be necessary to enable the sellers thereof to consummate the
            disposition of such Registrable Securities; and
<PAGE>
                                                                              15

      (n)   obtain (A) a cold comfort letter from the Company's independent
            accountants in customary form and covering such matters of the type
            customarily covered by cold comfort letters as the holders of a
            majority of Registrable Securities being sold pursuant to the
            applicable registration statement may reasonably request and (B) an
            opinion of the counsel representing the Company for the purposes of
            such registration, in form and substance as is customarily given to
            underwriters in an underwritten public offering.

      (o)   In the event of any underwritten public offering, cooperate with the
            Purchasers requesting registration, the underwriters participating
            in the offering and their counsel in any due diligence investigation
            reasonably requested by the Purchasers or the underwriters in
            connection therewith, and participate, to the extent reasonably
            requested by the underwriter for the offering or the Purchasers, in
            efforts to sell the Registrable Securities under the offering
            (including, without limitation, participating in "ROADSHOW" meetings
            with prospective investors) that would be customary for underwritten
            primary offerings of a comparable amount of equity securities by the
            Company;

      (p)   cooperate, to the extent reasonably requested, with each underwriter
            participating in the disposition of such Registrable Securities and
            their respective counsel in connection with any filings required to
            be made with the NASD; and

      (q)   take all other steps reasonably necessary to effect the registration
            of the Registrable Securities contemplated hereby.

            2.5 Registration on Form S-3. In addition to the rights set forth in
Sections 2.1 and 2.2, if the Purchasers request that the Company file a
registration statement on Form S-3 (or any successor form to Form S-3) for a
public offering of shares of Registrable Securities, and the Company is a
registrant entitled to use Form S-3 (or any successor form to Form S-3) to
register the Registrable Securities for such an offering, the Company shall use
its best efforts to cause such shares to be registered for the offering as soon
as practicable on Form S-3 (or any successor form to Form S-3). The procedures
and other limitations for effecting the registration of the Registrable
Securities on Form S-3 (or any successor form to Form S-3), including the
procedure used for any underwriting limitation, shall be as set forth in Section
2.1(b) above; provided, however, that (i) there shall not be any limit on the
number of registrations that may be requested by the Purchasers on Form S-3 (or
any successor form to Form S-3) and (ii) the Company shall not be obligated to
effect a registration under this Section 2.5 if the minimum estimated dollar
value of any offering of Registrable Securities pursuant to this Section 2.5 is
less than $1,000,000.

            2.6 Indemnification.
<PAGE>
                                                                              16

                  (a) The Company will indemnify each Purchaser, each of its
officers and directors and partners and such Purchaser's legal counsel, and each
Person controlling any such Persons within the meaning of Section 15 of the
Securities Act, with respect to which any registration, qualification or
compliance has been effected pursuant to this Agreement, and each underwriter,
if any, and each Person who controls any underwriter within the meaning of
Section 15 of the Securities Act, against all expenses, claims, losses, damages
and liabilities (or actions in respect thereof), including any of the foregoing
incurred in the investigation or settlement of any litigation, commenced or
threatened, arising out of or based on any untrue statement (or alleged untrue
statement) of a material fact contained in any registration statement,
prospectus, offering circular or other document, or any amendment or supplement
thereto, incident to any such registration, qualification or compliance, or
based on any omission (or alleged omission) to state therein a material fact
required to be stated therein or necessary to make the statements therein, not
misleading, or any violation by the Company of any rule or regulation
promulgated under the Securities Act or any state securities laws applicable to
the Company and relating to action or inaction required of the Company in
connection with any such registration, qualification or compliance, and will
reimburse each such Purchaser, each of its officers and directors and such
Purchaser's legal counsel, and each Person controlling any such Persons, each
such underwriter and each Person who controls any such underwriter, for any
legal and any other expenses reasonably incurred in connection with
investigating, preparing or defending any such claim, loss, damage, liability or
action, provided that the Company will not be liable in any such case to the
extent that any such claim, loss, damage, liability or expense arises out of or
is based on any untrue statement or omission or alleged untrue statement or
omission, made in reliance upon and in conformity with written information
furnished to the Company by an instrument duly executed by such Purchaser or
underwriter and stated to be specifically for use therein and provided, further,
that with respect to an untrue statement or omission or alleged untrue statement
or omission made in any preliminary prospectus or prospectus, the
indemnification provided for herein shall not apply to any loss, liability,
claim, damage or expense to the extent the same results from the sale of
Registrable Securities to a person to whom there was not sent or given, at or
prior to the written confirmation of such sale, a copy of the prospectus, or in
the case of an untrue statement or omission or alleged untrue statement or
omission in the prospectus, a copy of the amended prospectus or supplement
thereto, if the Company shall have previously furnished sufficient copies
thereof, based upon the number of copies requested by the Purchaser, to the
Purchaser a reasonable time in advance and the claim, damage or expense of such
person results from an untrue statement or alleged untrue statement or omission
or alleged omission of a material fact contained in a preliminary prospectus or
prospectus that was corrected in the prospectus or amendment or supplement
thereto.

                  (b) Each Purchaser will, if Registrable Securities held by
such Purchaser are included in the securities as to which such registration is
being effected, indemnify the Company, each of its directors and officers and
its legal counsel, each underwriter, if any, of the Company's securities covered
by such a registration statement, each Person who controls the Company or such
underwriter within the meaning of Section 15 of the Securities Act, and each
other such Purchaser, each of its officers and directors and each Person
controlling such Purchaser within the meaning of Section 15 of
<PAGE>
                                                                              17

the Securities Act, against all claims, losses, damages and liabilities (or
actions in respect thereof) arising out of or based on any untrue statement (or
alleged untrue statement) of a material fact contained in any such registration
statement, prospectus, offering circular or other document, or any omission (or
alleged omission) to state therein a material fact required to be stated therein
or necessary to make the statements therein not misleading, and will reimburse
the Company, such other Purchasers, such directors, officers, legal counsel,
underwriters or control Persons for any legal or any other expenses reasonably
incurred in connection with investigating or defending any such claim, loss,
damage, liability or action, in each case to the extent, but only to the extent,
that such untrue statement (or alleged untrue statement) or omission (or alleged
omission) is made in such registration statement, prospectus, offering circular
or other document in reliance upon and in conformity with written information
furnished to the Company by an instrument duly executed by such Purchaser and
stated to be specifically for use therein; provided, however, that the
obligation of such Purchaser hereunder shall be limited to an amount equal to
the proceeds received by such Purchaser upon the sale of the Registrable
Securities sold in the offering covered by such registration.

                  (c) Each party entitled to indemnification under this Section
2.6 (the "INDEMNIFIED PARTY") shall give notice to the party required to provide
indemnification (the "INDEMNIFYING PARTY") promptly after such Indemnified Party
has actual knowledge of any 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 that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or litigation, shall be
approved by the Indemnified Party (whose approval shall not unreasonably be
withheld). The Indemnified Party may participate in such defense at such party's
expense; provided, however, that the Indemnifying Party shall bear the expense
of such defense of the Indemnified Party if representation of both parties by
the same counsel would be inappropriate due to actual or potential conflicts of
interest (as determined in good faith by the Indemnified Party). The failure of
any Indemnified Party to give notice as provided herein shall not relieve the
Indemnifying Party of any liability it may have to an Indemnified Party (i)
otherwise than under this Section 2.6 or (ii) under this Section 2.6 except to
the extent that the Indemnifying Party forfeits substantive rights as defenses
by reason of such failure. No Indemnifying Party, in the defense of any such
claim or litigation, shall, except with the consent of each Indemnified Party,
consent to entry of any judgment or enter into any settlement which 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) The obligations of the Company and Purchasers under this
Section 2.6 shall survive the completion of any offering of Registrable
Securities under this Agreement.

                  (e) An Indemnifying Party shall make payments within thirty
(30) days upon receiving written confirmation from the Indemnified Party of the
nature and amount of the expenses to be indemnified.
<PAGE>
                                                                              18

                  (f) If the indemnification provided for in this Section 2.6 is
unavailable or insufficient to hold harmless an Indemnified Party, then each
Indemnifying Party shall contribute to the amount paid or payable to such
Indemnified Party as a result of the losses, claims, damages or liabilities
referred to in this Section 2.6 an amount or additional amount, as the case may
be, in such proportion as is appropriate to reflect the relative fault of the
Indemnifying Party or parties on the one hand and the Indemnified Party on the
other in connection with the statements or omissions which resulted in such
losses, claims, demands or liabilities as well as any other relevant equitable
considerations. The relative fault shall be determined by reference to, among
other things, whether the untrue or alleged untrue statement of a material fact
or the omission or alleged omission to state a material fact relates to
information supplied by the Indemnifying Party or parties on the one hand or the
Indemnified Party on the other and the parties' relative intent, knowledge,
access to information and opportunity to correct or prevent such untrue
statement or omission. The amount paid to an Indemnified Party as a result of
the losses, claims, damages or liabilities referred to in the first sentence of
this Section 2.6(f) shall be deemed to include any legal or other expenses
reasonably incurred by such Indemnified Party in connection with investigating
or defending any action or claim which is the subject of this Section 2.6. No
Person guilty of fraudulent misrepresentation (within the meaning of Section
11(f) of the Securities Act) shall be entitled to contribution from any Person
who was not guilty of such fraudulent misrepresentation.

                  (g) The indemnification provided for under this Agreement
shall remain in full force and effect regardless of any investigation made by or
on behalf of the Indemnified Party or any officer, director or controlling
Person of such Indemnified Party and shall survive the transfer of securities.

            2.7 Information by Purchaser. The Purchaser or Purchasers including
Registrable Securities in any registration shall furnish to the Company such
information regarding such Purchaser or Purchasers and the distribution proposed
by such Purchaser or Purchasers as the Company may reasonably request in writing
and as shall be required in connection with any registration, qualification or
compliance referred to in this Agreement.

            2.8 Rule 144 Reporting. With a view to making available the benefits
of certain rules and regulations of the Commission which may at any time permit
the sale of securities of the Company to the public without registration, after
such time as a public market exists for the Ordinary Shares of the Company, the
Company agrees to:

                  (a) Make and keep public information available, as those terms
are understood and defined in Rule 144 under the Securities Act, at all times
after the effective date of the first registration statement under the
Securities Act filed by the Company for an offering of its securities to the
general public;

                  (b) Use its best efforts to file with the Commission in a
timely manner all reports and other documents required of the Company under the
Securities
<PAGE>
                                                                              19

Act and the Securities Exchange Act of 1934, as amended (at any time after it
has become subject to such reporting requirements);

                  (c) So long as a Purchaser owns any Registrable Securities to
furnish to the Purchaser forthwith upon request a written statement by the
Company as to its compliance with the reporting requirements of said Rule 144
(at any time after 90 days after the effective date of the first registration
statement filed by the Company for an offering of its securities to the general
public), and of the Securities Act and the Securities Exchange Act of 1934, as
amended (at any time after it has become subject to such reporting
requirements), a copy of the most recent annual or quarterly report of the
Company, and such other reports and documents of the Company as a Purchaser may
reasonably request in availing itself of any rule or regulation of the
Commission allowing a Purchaser to sell any such securities without
registration.

            2.9 Transfer of Registration Rights. The rights to cause the Company
to register securities granted to Purchasers under Sections 2.1, 2.2 and 2.5 may
be assigned to a transferee or assignee in connection with the transfer or
assignment of any of the Registrable Securities held by a Purchaser on the date
hereof, provided, that (i) such transfer may otherwise be effected in accordance
with applicable securities laws, (ii) the Company is given reasonably prompt
written notice of such assignment, (iii) the transferee or assignee agrees in
writing to be bound by the obligations of this Agreement, and (iv) the
transferee (a) receives at least 25,000 Ordinary Shares or Preferred Shares
convertible into 25,000 Ordinary Shares, in each case subject to adjustment for
share splits, share dividends or other similar changes in capitalization, or (b)
is a general or limited partner of, an Affiliate of or holder of beneficial
interests in the transferor.

            2.10 General. In the event the Company is obligated to effect a
public offering, the Company, the Purchasers and the Stockholders shall cause
such meetings to be held, votes cast, resolutions passed, by-laws enacted,
documents executed and all acts and things done to effect the public offering on
customary and usual terms.

            2.11 Other Registration Rights. The Company shall not grant to any
Person any registration rights except with the consent of the Supermajority
Purchasers, so long as any of the registration rights under this Agreement
remain in effect; provided, that the Company may grant registration rights
without such consent so long as such rights could not result in a reduction in
the number of securities that the Purchasers may include in an underwritten
public offering pursuant to this Agreement or otherwise adversely affect the
rights of the Purchasers under this Agreement.

            2.12 Lock-up Agreements. Each Purchaser and Stockholder hereby
agrees that such Purchaser and Stockholder shall not sell any Ordinary Shares
(or other securities) of the Company held by such Purchaser and Stockholder
(other than those included in the registration) for a period specified by the
representative of the underwriters of Ordinary Shares (or other securities) of
the Company not to exceed one hundred eighty (180) days following an initial
public offering of the Company's securities; provided that all executive
officers and directors of the Company enter into similar agreements.
<PAGE>
                                                                              20

            2.13 Mergers, Etc. The Company shall not, directly or indirectly,
enter into any merger, consolidation or reorganization in which the Company
shall not be the surviving corporation unless the proposed surviving corporation
shall, prior to such merger, consolidation or reorganization, agree in writing
to assume the obligations of the Company under this Agreement, and for that
purpose references hereunder to "REGISTRABLE SECURITIES" shall be deemed to be
references to the securities which the Purchasers would be entitled to receive
in exchange for Registrable Securities under any such merger, consolidation or
reorganization, provided, however, that the provisions of this Agreement shall
not apply in the event of any merger, consolidation or reorganization in which
the Company is not the surviving corporation if the Purchasers are entitled to
receive in exchange therefor (i) cash or (ii) securities of the acquiring
corporation which may be immediately sold to the public pursuant to an effective
registration statement under the Securities Act or pursuant to an exemption
therefrom which permits sales without limitation as to volume or the manner of
sale on a nationally recognized exchange in the United States or on the Nasdaq
National Market.

            2.14 Termination. The rights granted pursuant to this Section 2
shall terminate upon the tenth (10th) anniversary of the consummation of a
Qualified IPO.

                                   SECTION 3

                      AFFIRMATIVE COVENANTS OF THE COMPANY,
                       THE PURCHASERS AND THE STOCKHOLDERS

            3.1 Board Representation and Voting Agreement.

                  (a) From and after the date hereof, each Stockholder and each
Purchaser shall vote all of the voting securities of the Company (including the
Ordinary Shares) over which such Person has voting control and shall take all
other necessary or desirable actions within his or its control (whether in his
or its capacity as a stockholder, director, member of a board committee or
officer of the Company or otherwise, and including, without limitation,
attendance at meetings in person or by proxy for purposes of obtaining a quorum
and execution of written consents or resolutions in lieu of meetings), and the
Company shall take all necessary or desirable actions within its control
(including, without limitation, calling special board and shareholders'
meetings) so that:

      (i)   Subject to the provisions of clause (iv) and (v) below, the
            authorized number of directors of the Company's Board of Directors
            (the "Board") shall be established at eight (8) directors and a
            quorum of the Board shall be four (4) directors;

      (ii)  Subject to the provisions of clause (iv) below, the designees
            specified below shall be elected to the Board and to any committees
            thereof at each election of directors during the term of this
            Agreement, such designees initially to be the following:
<PAGE>
                                                                              21

            (A)   One person designated by the Founders (the "FOUNDERS'
                  DIRECTOR"), who shall initially be Andrea Corcoran;

            (B)   Two persons designated by BBB (the "SERIES A DIRECTORS"), who
                  shall initially be Dr. Ansbert Gadicke and Paul Brooke;

            (C)   One person designated by TVM (the "SERIES B DIRECTOR"), who
                  shall initially be Dr. Alexandra Goll;

            (D)   One person (the "SERIES C DIRECTOR") designated (1) for so
                  long as Affiliates of Credit Suisse First Boston Private
                  Equity shall hold at least 75% of the Series C Preferred
                  Shares purchased by them pursuant to the Purchase Agreement,
                  by Credit Suisse First Boston Equity Partners, L.P. or (2) at
                  such time as (i) above is not applicable, then by a majority
                  of the holders of the Series C Preferred Shares, who shall
                  initially be Michael Schmertzler.

            (E)   The Chief Executive Officer of the Company, Dr. Jean-Pierre
                  Sommadossi; and

            (F)   Two industry experts who are not employees of the Company, one
                  of whom shall be jointly designated by BBB, TVM, and the
                  Founders' Director, who shall initially be Dr. Marie Warburg,
                  and one of whom shall be designated by Nomura, subject to the
                  approval of BBB, TVM and the Founders' Director.

      (iii) In the event that any representative designated hereunder for any
            reason ceases to serve as a member of the Board or any committee
            thereof during such representative's term of office, the parties who
            designated such representative shall designate the person to fill
            the resulting vacancy on the Board or committee;

      (iv)  by the date six months from the date hereof (or, in the event no
            such action is taken by such date, in any event prior to an initial
            public offering by the Company of Ordinary Shares) the authorized
            number of directors of the Board shall be reduced in number from
            eight (8) to seven (7) directors, which shall comprise at least two
            industry experts who are not employees of the Company and the Series
            C Director and a quorum of the Board shall be four (4) directors;
            and

      (v)   At any time after April 24, 2004, but before a Qualified IPO, the
            Supermajority Purchasers may deliver to the Company a "LIQUIDITY
            NOTICE," whereupon the primary mandate of the Board shall be to
            effect a Sale of the Company, a Qualified IPO or such other
            opportunity acceptable to the Supermajority Purchasers for
            stockholders to realize liquidity with respect to their capital
            stock in the Company. If the Company shall not have entered into a
            definitive agreement with respect to such a transaction (i.e., a
            purchase and sale agreement, firm
<PAGE>
                                                                              22

            commitment underwriting agreement, etc.) within six months of the
            delivery of such Liquidity Notice, then the authorized number of
            directors of the Board shall be established at nine (9), a quorum of
            the Board shall be five (5) directors and the additional members of
            the Board shall be individuals designated by the Supermajority
            Purchasers.

                  (b) Each and every transferee or assignee of the shares from
any Stockholder or Purchaser shall be bound by and subject to all the terms and
conditions of this Section 3.1. So long as the provisions of this Section 3.1
are in effect, the Company shall require, as a condition precedent to the
transfer of any shares covered by this Section 3.1, that the transferee agrees
in writing to be bound by, and subject to, the terms and conditions of this
Section 3.1 as provided in this Section 3.1 and to ensure that his transferees
of the shares shall be likewise bound.

                  (c) The Company, the Purchasers and the Stockholders agree
that, so long as the provisions of this Section 3 or of Sections 4 or 5 below
are in effect, all share certificates in respect of Ordinary Shares, Registrable
Securities or other voting securities, now or hereafter held by each Stockholder
will be stamped or otherwise imprinted with a legend in substantially the
following form:

            THE SHARES EVIDENCED BY THIS CERTIFICATE ARE SUBJECT TO AGREEMENTS,
            COVENANTS AND RESTRICTIONS IN REGARD TO THE VOTING OF SUCH SHARES
            AND THEIR TRANSFER, AS PROVIDED IN THE PROVISIONS OF A SECOND
            AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT DATED APRIL 24, 2001 BY
            AND AMONG THE COMPANY AND THE SHAREHOLDERS NAMED THEREIN, A COPY OF
            WHICH IS ON FILE IN THE OFFICE OF THE SECRETARY OF THE COMPANY.

                  (d) Each of the parties acknowledges that all other parties
hereto will be irreparably damaged in the event that the provisions of this
Section are not specifically enforced. Accordingly, should any dispute arise
pursuant to Section 3.1 of this Agreement, the parties agree that a decree of
specific performance shall be an appropriate remedy. Such remedy shall be
cumulative and shall be in addition to any other remedies which any party may
have at law or in equity.

                  (e) The Company shall pay the reasonable out-of-pocket travel,
lodging and other related expenses of all directors elected pursuant to Section
3.1 incurred in connection with attendance at meetings of the Board or any
committee thereof. If the director designated by Nomura pursuant to Section
3.1(a)(ii)(E) above shall request a fee for serving as a director of the
Company, the Board shall determine and authorize payment of the appropriate fee
based on such designee's experience and industry record and the standard in the
industry with respect to such fees.

            3.2 Voting and Sale or Tender of Shares. In the event the
Supermajority Purchasers deliver a Liquidity Notice to the Company or elect to
appoint additional directors as provided for in Section 3.1(a)(iv), each
Purchaser and each
<PAGE>
                                                                              23

Stockholder shall take all necessary or desirable action with respect to the
securities over which such Person exercises control (including, without
limitation, the removal and election of directors, attendance at stockholders'
meetings in person or by proxy for the purposes of obtaining a quorum and the
execution of written consents in lieu of meetings) such that any proposal or
resolution requested by the Supermajority Purchasers in connection with actions
taken pursuant to the Liquidity Notice (a "PURCHASER SALE OF THE COMPANY") shall
be implemented by the Company and if the Company's shareholders are entitled to
vote on any such matter, whether by law, under the Company's Charter or
otherwise, all of the voting securities of the Company (including the Ordinary
Shares) over which such Purchaser or Stockholder has voting control shall be
voted in favor of the proposal or resolution in connection with the Purchaser
Sale of the Company or appointment of an additional director pursuant to Section
3.1(a)(iv), as the case may be, being proposed by the Supermajority Purchasers.
Each Purchaser and each Stockholder shall sell or tender the Ordinary Shares and
other equity securities of the Company held by him or it and otherwise take all
action necessary and desirable in connection with the consummation of a
Purchaser Sale of the Company, on the terms and conditions approved by the Board
of Directors and the Supermajority Purchasers. Each Purchaser and each
Stockholder will bear its pro rata share (based upon the number of Ordinary
Shares held on an as converted and fully diluted basis) of the cost of any sale
of Ordinary Shares or other equity securities pursuant to a Purchaser Sale of
the Company to the extent such costs are incurred for the benefit of all
stockholders and are not otherwise paid by the Company or the acquiring party.
Costs incurred by Purchasers or Stockholders on their own behalf will not be
considered costs of the transaction hereunder.

            3.3 Termination. The rights granted pursuant to this Section 3 shall
terminate immediately prior to the consummation of a Qualified IPO.

                                   SECTION 4

                               PREEMPTIVE RIGHTS

            4.1 Right to Purchase. The Company shall only issue New Shares in
accordance with the following terms:

                  (a) In the event the Company desires to issue any New Shares,
it shall first deliver to each Purchaser a written notice (the "NOTICE OF
PROPOSED ISSUANCE") specifying the type and total number of such New Shares
which the Company then desires to issue (the "OFFERED NEW SHARES"), all of the
terms, including the price, upon which the Company proposes to issue the Offered
New Shares, and stating that the Purchasers shall have the right to purchase the
Offered New Shares in the manner specified in this Section 4.1 at the price and
in accordance with the terms and provisions specified in such Notice of Proposed
Issuance.

                  (b) During the thirty (30) consecutive day period commencing
on the date all Purchasers have received the Notice of Proposed Issuance (the
"THIRTY DAY Period"), the Purchasers shall have the option to purchase all or
any portion of the
<PAGE>
                                                                              24

Offered New Shares at the price and terms specified in the Notice of Proposed
Issuance. Each Purchaser electing to purchase Offered New Shares must give
written notice of its election to the Company during such Thirty Day Period.

                  (c) Each Purchaser shall have the right to purchase that
number of the Offered New Shares as shall be equal to the number of the Offered
New Shares multiplied by a fraction, the numerator of which shall be the number
of Ordinary Shares (calculated on an as converted basis) then owned by such
Purchaser and the denominator of which shall be the aggregate number of Ordinary
Shares (calculated on an as converted basis) then owned by all of the
Purchasers. The amount of such Offered New Shares that each Purchaser is
entitled to purchase under this Section 4.1 shall be referred to as its
"PROPORTIONATE SHARE."

                  (d) Each Purchaser shall have a right of oversubscription such
that if any other Purchaser fails to elect to purchase his or its full
Proportionate Share of the Offered New Shares, the other Purchaser(s) shall,
among them, have the right to purchase up to the balance of such Offered New
Shares not so purchased. The Purchasers may exercise such right of
oversubscription by electing to purchase more than their Proportionate Shares of
the Offered New Shares by so indicating in their written notice given during the
Thirty Day Period. If, as a result thereof, such oversubscriptions exceed the
total number of the Offered New Shares available in respect to such
oversubscription privilege, the oversubscribing Purchasers shall be cut back
with respect to oversubscriptions on a pro rata basis in accordance with their
respective Proportionate Shares or as they may otherwise agree among themselves.

                  (e) If all of the Offered New Shares have not been purchased
by the Purchasers pursuant to paragraphs (a)-(d) hereof, then the Company shall
have the right, subject to Section 4.4 hereof, until the expiration of
one-hundred eighty (180) consecutive days commencing on the first day
immediately following the expiration of the Thirty Day Period, to issue any
remaining Offered New Shares at not less than, and on terms no more favorable to
the purchaser than, the price and such other terms as are specified in the
Notice of Proposed Issuance. If for any reason such Offered New Shares are not
issued within such period and at such price and on such terms, the right to
issue in accordance with the Notice of Proposed Issuance shall expire and the
provisions of this Agreement shall continue to be applicable to the Offered New
Shares.

                  (f) The Purchaser purchasing the greatest percentage of the
Offered New Shares shall set the place, time and date for the closing of the
purchase of the Offered New Shares, which closing shall not be more than 20 days
after the first day immediately following the expiration of the Thirty Day
Period.

            4.2 Price. The purchase price for the Offered New Shares shall,
unless otherwise agreed in writing by the parties to such transaction, be paid
on the date of closing in cash, by certified check or by wire transfer of
immediately available funds to a bank account designated in advance by the
Company.
<PAGE>
                                                                              25

            4.3 Closing. At the closing, the Purchasers shall deliver the
consideration required by Section 4.2 and the Company shall deliver certificates
representing the Offered New Shares.

            4.4 Termination. The rights granted pursuant to this Section 4 shall
terminate immediately prior to the consummation of a Qualified IPO or a
Qualified Private Offering.

                                   SECTION 5

                        RESTRICTIONS ON TRANSFER; CO-SALE

            5.1 Restrictions.

                  (a) No Stockholder shall Transfer any Ordinary Shares or other
equity securities of the Company except (i) as may be otherwise specifically
approved in writing by the Supermajority Purchasers and (ii) if so approved, in
accordance with the Purchasers' right of first refusal pursuant to Section 5.2
below and right of co-sale pursuant to Section 5.3 below; and provided, further,
that in connection with any Transfer under this Section 5.1, the transferee
shall hold such Ordinary Shares or other equity securities of the Company
subject to the same restrictions applicable to its transferor and shall agree to
be bound by the terms of this Agreement.

                  (b) The provisions of Section 5.1(a) shall not apply to (i) a
Transfer to a Family Member of a Stockholder for estate planning purposes or
(ii) a Transfer by testamentary or intestate disposition.

                  (c) The rights granted pursuant to Section 5.1(a) shall
terminate upon the earliest to occur of (i) the redemption or conversion of all
of the outstanding Preferred Shares and (ii) immediately prior to the
consummation of a Qualified IPO; provided, however, that the right of approval
granted in Section 5.1(a)(i) shall not terminate until the date that is one year
after the consummation of a Qualified IPO with respect to any Transfer of equity
securities of the Company by any Founder or by Giles Gosselin.

            5.2 Right of First Refusal Applicable to Stockholders.

                  (a) If at any time a Stockholder (a "TRANSFERRING
STOCKHOLDER") desires to Transfer his Ordinary Shares or other equity securities
of the Company to a third party (the "PROPOSED TRANSFEREE") and such Transfer
has been approved by the Supermajority Purchasers in accordance with Section 5.1
hereof, then notwithstanding that such approval was obtained, the Transferring
Stockholder shall, at least thirty (30) days prior to any Transfer, submit a
written offer (the "OFFER") to sell such Ordinary Shares or other securities of
the Company (the "OFFERED SHARES") to the Purchasers and the Company on terms
and conditions, including price, not less favorable to the Purchasers and the
Company than those on which the Transferring Stockholder proposes to Transfer
such Offered Shares to the Proposed Transferee, and shall send a copy of the
offer to the other Stockholders. The Offer shall disclose the identity of the
<PAGE>
                                                                              26

Proposed Transferee, the Offered Shares proposed to be sold, the total number of
Ordinary Shares and other securities of the Company owned by the Transferring
Stockholder, the terms and conditions, including price, of the proposed
Transfer, and any other material fact relating to the proposed Transfer. The
Offer shall further state that the Purchasers or the Company may acquire, in
accordance with the provisions of this Agreement, any or all of the Offered
Shares for the price and upon the other terms and conditions, including deferred
payment (if applicable), set forth therein.

                  (b) Each Purchaser shall have the right to purchase that
number of Offered Shares as shall be equal to the number of Offered Shares
multiplied by a fraction, the numerator of which shall be the number of Ordinary
Shares (calculated on an as converted basis) then owned by such Purchaser and
the denominator of which shall be the aggregate number of Ordinary Shares
(calculated on an as converted basis) then owned by all of the Purchasers. The
amount of such Offered Shares that each Purchaser is entitled to purchase under
this Section 5.2 shall be referred to as its "PRO RATA SHARE." If a Purchaser
desires to purchase Offered Shares, such Purchaser shall communicate in writing
its election to purchase to the Transferring Stockholder and to the Company,
which communication shall indicate the number of Offered Shares that the
Purchasers elect to purchase and shall be given to the Transferring Stockholder
and to the Company within fifteen (15) days of the date the Offer was made (the
"15-DAY PERIOD").

                  (c) Each Purchaser shall have a right of oversubscription such
that if any other Purchaser fails to elect to purchase his or its full Pro Rata
Share of the Offered Shares, the other Purchaser(s) shall, among them, have the
right to purchase up to the balance of such Offered Shares not so purchased.
Each Purchaser may exercise such right of oversubscription by electing to
purchase more than its Pro Rata Share of the Offered Shares by so indicating in
its written notice given during the 15-Day Period. If, as a result thereof, such
oversubscriptions exceed the total number of the Offered Shares available in
respect to such oversubscription privilege, the oversubscribing Purchasers shall
be cut back with respect to oversubscriptions on a pro rata basis in accordance
with their respective Pro Rata Shares or as they may otherwise agree among
themselves.

                  (d) If the Purchasers do not elect to purchase all of the
Offered Shares, then the Company may elect to purchase up to the balance of
Offered Shares by communicating in writing to the Transferring Stockholder and
the Purchasers the number of Offered Shares that the Company elects to purchase,
which notice shall be given to the Transferring Stockholders and the Purchasers
within five (5) days of the date the acceptance from the Purchasers was made or
if no such acceptance was made, on the fifth day after expiration of the Offer
Period. Such communications shall, when taken in conjunction with the Offer, be
deemed to constitute valid, legally binding and enforceable agreements for the
sale and purchase of such Offered Shares. Sales of the Offered Shares to be sold
to the Purchasers and the Company pursuant to this Section 5.2 shall be made on
the 30th day following the date the Offer was made (or if such 30th day is not a
business day, then on the next succeeding business day). Such sales shall be
effected by the Transferring Stockholder's delivery to the Purchasers and
Company of a certificate or certificates evidencing the Offered Shares to be
purchased by them, together with duly executed instruments of transfer in favor
of the Purchasers and Company (or as they may
<PAGE>
                                                                              27

direct), against payment to the Transferring Stockholder of the purchase price
therefor by the Purchasers and Company.

                  (e) If the Purchasers and the Company do not purchase all of
the Offered Shares and subject to the Co-Sale rights provided for under Section
5.3 below, any remaining Offered Shares may be sold by the Transferring
Stockholder at any time within 120 days after the date the Offer was made. Any
such sale shall be to the Proposed Transferee or another Stockholder, at not
less than the price and upon other terms and conditions, if any, not more
favorable to the Proposed Transferee or other Stockholder than those specified
in the Offer. Any Offered Shares not sold within such 120-day period shall
continue to be subject to the requirements of a prior offer pursuant to this
Section 5.

                  (f) The rights granted pursuant to this Section 5.2 shall not
apply to (i) a Transfer to a Family Member of a Stockholder for estate planning
purposes, (ii) a Transfer by testamentary or intestate disposition.

                  (g) The rights granted pursuant to this Section 5.2 shall
terminate immediately prior to the consummation of a Qualified IPO or a
Qualified Private Offering.

                  (h) In connection with any sale pursuant to this Section 5.2,
the transferee shall hold such Ordinary Shares or other equity securities of the
Company subject to the same restrictions applicable to the Stockholders and
shall agree to be bound by the terms of this Agreement.

            5.3 Right of Co-Sale Applicable to Stockholders.

                  (a) After receiving the Offer delivered pursuant to Section
5.2(a) above, the Purchasers (each a "CO-SALE PARTICIPANT") may, in lieu of
exercising any rights of first refusal they may have under Section 5.2, elect to
participate in the contemplated Transfer by delivering written notice to the
Transferring Stockholder within fifteen days after delivery of the Offer. Each
Co-Sale Participant shall be entitled to sell in the contemplated Transfer, at
the same price and on the same terms, a number of Ordinary Shares or other
equity securities of the Company (on an Ordinary Share equivalent basis) equal
to the product of (i) the quotient determined by dividing (A) the number of
outstanding Ordinary Shares (calculated on an as converted basis) owned by such
Co-Sale Participant by (B) the aggregate number of outstanding Ordinary Shares
owned or held by the Transferring Stockholder and all of the Co-Sale
Participants (calculated on an as converted basis) and (ii) the number of
Offered Shares (on an Ordinary Share equivalent basis) to be sold in the
contemplated Transfer.

                  (b) The provisions of Section 5.3(a) shall not apply to (i) a
Transfer to a Family Member of a Stockholder for estate planning purposes or
(iii) a Transfer by testamentary or intestate disposition.
<PAGE>
                                                                              28

                  (c) The rights granted pursuant to this Section 5.3 shall
terminate immediately prior to the consummation of a Qualified IPO or a
Qualified Private Offering.

                  (d) In connection with any sale pursuant to this Section 5.3,
the transferee shall hold such Ordinary Shares or other equity securities of the
Company subject to the same restrictions applicable to the Stockholders and
shall agree to be bound by the terms of this Agreement.

            5.4 Right of First Refusal Applicable to Purchasers. For purposes of
this Section 5.4 only, the term "Purchasers" shall not include the holders of
Series C Preferred Shares (or Ordinary Shares issued upon conversion thereof)
with respect to any such shares, provided that: (i) such holders shall be sent a
copy of any Preferred Offer (as defined herein) for purposes associated with
their rights under Section 5.5 hereof and (ii) to the extent holders of Series C
Preferred Shares are intending to transfer such Series C Shares (or the Ordinary
Shares into which any Series C Preferred Shares have been converted) to a
Competitor, other than any Person who is a Purchaser or Stockholder immediately
after the Closing Date, the provisions set forth below will be applicable to
such intended transfer.

                  (a) If at any time a Purchaser (a "TRANSFERRING PURCHASER")
desires to transfer its Preferred Shares (or the Ordinary Shares into which they
have been converted) to a third party (the "PROPOSED BUYER"), then the
Transferring Purchaser shall, at least ten (10) days prior to any Transfer,
submit a written offer (the "PREFERRED OFFER") to sell such Preferred Shares or
the Ordinary Shares into which they are converted (the "OFFERED SECURITIES") to
the other Purchasers on terms and conditions, including price, not less
favorable to such Purchasers than those on which the Transferring Purchaser
proposes to transfer such Offered Securities to the Proposed Buyer. The
Preferred Offer shall disclose the identity of the Proposed Buyer, the Offered
Securities proposed to be sold, the terms and conditions, including price, of
the Proposed Transfer, and any other material fact relating to the proposed
Transfer. The Preferred Offer shall further state that the Purchasers may
acquire, in accordance with the provisions of this Agreement, all of the Offered
Securities for the price and upon the other terms and conditions, including
deferred payment (if applicable), set forth therein.

                  (b) Each Purchaser shall have the right to purchase that
number of Offered Securities as shall be equal to the number of Offered
Securities multiplied by a fraction, the numerator of which shall be the number
of Ordinary Shares (calculated on an as converted basis) then owned by such
Purchaser and the denominator of which shall be the aggregate number of Ordinary
Shares (calculated on an as converted basis) then owned by all of the Purchasers
other than the Transferring Purchaser. The amount of such Offered Securities
that each Purchaser is entitled to purchase under this Section 5.4 shall be
referred to as its "PRO RATA PORTION." If a Purchaser desires to purchase
Offered Securities, such Purchaser shall communicate in writing its election to
purchase to the Transferring Purchaser, which communication shall indicate the
number of Offered Securities that the Purchaser elects to purchase and shall be
given to the Transferring Purchaser within ten (10) days of the date the Offer
was made (the "10-DAY PERIOD").
<PAGE>
                                                                              29

                  (c) Each Purchaser shall have a right of oversubscription such
that if any other Purchaser fails to elect to purchase his or its full Pro Rata
Portion of the Offered Securities, the other Purchaser(s) shall, among them,
have the right to purchase up to the balance of such Offered Securities not so
purchased. Each Purchaser may exercise such right of oversubscription by
electing to purchase more than its Pro Rata Portion of the Offered Securities by
so indicating in its written notice given during the 10-Day Period. If, as a
result thereof, such oversubscriptions exceed the total number of the Offered
Securities available in respect to such oversubscription privilege, the
oversubscribing Purchasers shall be cut back with respect to oversubscriptions
on a pro rata basis in accordance with their respective Pro Rata Portions or as
they may otherwise agree among themselves.

                  (d) The communications described above shall, when taken in
conjunction with the Preferred Offer, be deemed to constitute valid, legally
binding and enforceable agreements for the sale and purchase of such Offered
Securities. Sales of the Offered Securities to be sold to the other Purchasers
pursuant to this Section 5.4 shall be made on the 20th day following the date
the Preferred Offer was made (or if such 20th day is not a business day, then on
the next succeeding business day). Such sales shall be effected by the
Transferring Purchaser's delivery to the other Purchasers of a certificate or
certificates evidencing the Offered Securities to be purchased by them, together
with duly executed instruments of transfer in favor of such Purchasers (or as
they may direct), against payment to the Transferring Purchaser of the purchase
price therefor by such Purchasers.

                  (e) If the Purchasers other than the Transferring Purchaser do
not agree to purchase all of the Offered Securities and subject to the Co-Sale
rights provided for under Section 5.5 below, the Offered Securities may be sold
by the Transferring Purchaser at any time within 120 days after the date the
Preferred Offer was made. Any such sale shall be to the Proposed Buyer, at not
less than the price and upon other terms and conditions, if any, not more
favorable to the Proposed Buyer than those specified in the Preferred Offer. Any
Offered Securities not sold within such 120-day period shall continue to be
subject to the requirements of a prior offer pursuant to this Section 5.4.

                  (f) The rights granted pursuant to this Section 5.4 shall not
apply to a Transfer to an Affiliate.

                  (g) The rights granted pursuant to this Section 5.4 shall
terminate immediately prior to the consummation of a Qualified IPO or a
Qualified Private Offering.

                  (h) In connection with any sale pursuant to this Section 5.4,
the transferee shall hold such Preferred Shares subject to the same restrictions
applicable to the Purchasers and shall agree to be bound by the terms of this
Agreement.

            5.5 Right of Co-Sale Applicable to the Purchasers and Stockholders.
For the avoidance of doubt, for purposes of this Section 5.5, the term
"PURCHASERS" shall
<PAGE>
                                                                              30

include holders of Series C Preferred Shares (or Ordinary Shares issued upon
conversion thereof).

                  (a) If one or more Purchasers or Stockholders propose to sell
Offered Securities and/or Offered Shares constituting more than twenty-five
percent (25%) of the Company's then outstanding Ordinary Shares (calculated on
an as converted basis), the Purchasers (each a "CO-SELLER") may, in lieu of
exercising any rights of first refusal they may have under Section 5.4, elect to
participate in the contemplated Transfer by delivering written notice to the
Transferring Purchaser and/or Transferring Stockholder within fifteen days after
delivery of the Preferred Offer. Each Co-Seller shall be entitled to sell in the
contemplated Transfer, at the same price and on the same terms, a number of
Preferred Shares or other equity securities of the Company (on an Ordinary Share
equivalent basis) equal to the product of (i) the quotient determined by
dividing (A) the number of outstanding Ordinary Shares (calculated on an as
converted basis) owned by such Co-Seller by (B) the aggregate number of
outstanding Ordinary Shares owned or held by the Transferring Purchaser and/or
Transferring Stockholder and all of the Co-Sellers (calculated on an as
converted basis) and (ii) the number of Offered Securities and Offered Shares
(on an Ordinary Share equivalent basis) to be sold in the contemplated Transfer.

                  (b) The provisions of Section 5.5(a) shall not apply to a
Transfer to an Affiliate.

                  (c) The rights granted pursuant to this Section 5.5 shall
terminate immediately prior to the consummation of a Qualified IPO or a
Qualified Private Offering.

                  (d) In connection with any sale pursuant to this Section 5.5,
the transferee shall hold such Preferred Shares or other equity securities of
the Company subject to the same restrictions applicable to the Purchasers and
shall agree to be bound by the terms of this Agreement.

                                   SECTION 6

                                 CONFIDENTIALITY

            6.1 Confidentiality. Under no circumstances and at no time during or
after the term of this Agreement will a Stockholder or Purchaser directly or
indirectly, disclose, divulge, render, offer or use any knowledge or information
with respect to the affairs or plans of the Company or any of its Subsidiaries,
except (i) in the course of the proper performance of its or his duties
hereunder (ii) in accordance with any obligation it may have pursuant to
applicable law or agreements with its Affiliates in connection with its
investment in the Company (including, without limitation, the obligation of any
Purchaser to deliver financial information to its general and limited partners);
provided that such Affiliates are bound in writing to protect the
confidentiality of such information or (iii) unless otherwise in the public
domain, and each Stockholder or Purchaser acknowledges and agrees that any and
all such information will be received by him or it
<PAGE>
                                                                              31

and held by each such respective Persons or such other Persons as permitted by
clause (ii) above in a confidential capacity.

            6.2 Enforcement. The Company, each Purchaser and each Stockholder
agree that the covenants set forth in this Section 6 shall be enforced to the
fullest extent permitted by law and equity and may include specific performance
and injunctive and other equitable relief.

                                   SECTION 7

                                  MISCELLANEOUS

            7.1 Waivers and Amendments. The rights and obligations of the
Company, the Purchasers and the Stockholders under this Agreement may not be
waived (either generally or in a particular instance, either retroactively or
prospectively, and either for a specified period of time or indefinitely) or
amended without the written consent of (i) the holders of 85% of the Ordinary
Shares issued or issuable upon conversion of the Preferred Shares including,
with respect to Section 5.4 or 5.5, the written consent of Nomura and (ii)
Stockholders holding a majority of the Ordinary Shares owned by such
Stockholders. Upon the effectuation of each such waiver or amendment, the
Company shall promptly give written notice thereof to the holders of the shares
who have not previously consented thereto in writing.

            7.2 Governing Law. This Agreement shall be governed by and construed
under the laws of the State of New York as such laws are applied to contracts
made and to be fully performed entirely within that state between residents of
that state.

            7.3 Successors and Assigns. Except as otherwise expressly provided
herein, the provisions hereof shall inure to the benefit of, and be binding
upon, the successors, assigns, heirs, executors and administrators of the
parties hereto.

            7.4 Entire Agreement. This Agreement constitutes the full and entire
understanding and agreement between the parties with regard to the subject
matter hereof.

            7.5 Notices. All notices and other communications required or
permitted hereunder shall be in writing and shall be personally delivered or
sent by facsimile machine (with a confirmation copy sent by one of the methods
authorized in this Section or by U.S. airmail to locations outside the United
States), commercial (including without limitation FedEx) or U.S. Postal Service
overnight delivery service, or, if the recipient's address is within the United
States, deposited with the U.S. Postal Service mailed first class, addressed (a)
to such Stockholder's or Purchaser's address set forth in Schedule A hereto, or
to such other address as such Stockholder or Purchaser shall have furnished to
the Company in writing, or (b) if to the Company, to 125 Cambridge Park Drive,
Cambridge, MA 02140, or to such other address as the Company shall have
furnished to the Stockholders and Purchasers in writing.
<PAGE>
                                                                              32

            Notices shall be deemed given upon the earlier to occur of (i)
receipt by the party to whom such notice is directed; (ii) if sent by facsimile
machine, on the day (other than a Saturday, Sunday or legal holiday in the
jurisdiction to which such notice is directed) such notice is sent if sent (as
evidenced by the facsimile confirmed receipt) prior to 5:00 p.m. Eastern Time
and, if sent after 5:00 p.m. Eastern Time, on the day (other than a Saturday,
Sunday or legal holiday in the jurisdiction to which such notice is directed)
after which such notice is sent; (iii) on the first business day (other than a
Saturday, Sunday or legal holiday in the jurisdiction to which such notice is
directed) following the day the same is deposited with the commercial carrier if
sent by commercial overnight delivery service; or (iv) the fifth day (other than
a Saturday, Sunday or legal holiday in the jurisdiction to which such notice is
directed) following deposit thereof with the U.S. Postal Service as aforesaid.
Each party, by notice duly given in accordance herewith, may specify a different
address for the giving of any notice hereunder.

            7.6 Severability. In case any provision of this Agreement shall be
invalid, illegal or unenforceable, the validity, legality and enforceability of
the remaining provisions of this Agreement shall not in any way be affected or
impaired thereby.

            7.7 Titles and Subtitles. The titles of the sections and subsections
of this Agreement are for convenience of reference only and are not to be
considered in construing this Agreement.

            7.8 Counterparts. This Agreement may be executed in any number of
counterparts, each of which shall be an original, but all of which together
constitute one instrument.

            7.9 Consent to Jurisdiction. The Company, each Purchaser and each
Stockholder hereby agree to submit to the exclusive jurisdiction of the courts
in and of the Commonwealth of Massachusetts (including the federal courts
therein) and to the courts to which an appeal of the decisions of such courts
may be taken, and consent that service of process with respect to all courts in
and of the Commonwealth of Massachusetts may be made by registered mail to it at
the address set forth on Schedule A hereto.

            7.10 Authorization of Preferred Shares. The holders of the Ordinary
Shares hereby agree and consent to the creation and allotment of the Series C
Preferred Shares pursuant to the Members resolution dated April 20, 2001.

            7.11 Filing of this Agreement. The Company and each Stockholder
hereby agree to take all necessary actions (including without limitation an
amendment to the Charter) to effect the filing of this Agreement with the
Charter of the Company as soon as practicable after the date hereof.

            7.12 Additional Ordinary Shares; Joinder.
<PAGE>
                                                                              33

                  (a) In the event additional Ordinary Shares are issued by the
Company to a Stockholder at any time during the term of this Agreement, either
directly or upon the exercise or exchange of securities of the Company
exercisable for or exchangeable into Ordinary Shares, such additional Ordinary
Shares shall, as a condition to such issuance, be deemed subject to the terms
and provisions of this Agreement.

                  (b) In the event that more than 60,000 Ordinary Shares are
issued by the Company to any Person or any person otherwise becomes a holder of
more than 60,000 Ordinary Shares at any time during the term of this Agreement,
either directly or upon the conversion, exercise of exchange of securities of
the Company convertible into or exercisable or exchangeable for Ordinary Shares
(including options), such Person, as a condition to receiving such Ordinary
Shares, shall be deemed a Stockholder for purposes of this Agreement with
respect to such Ordinary Shares and be bound by and subject to the terms and
provisions of this Agreement and, if not already a signatory to this Agreement
as a Stockholder, such Person shall execute and deliver to the Company a
Stockholder Joinder in the form of Exhibit 1 attached hereto.

            7.13 Additional Purchasers. Persons that, after the date hereof,
purchase Series C Preferred Shares and Series C Warrants pursuant to the
Purchase Agreement and become "Purchasers" thereunder may, with the prior
written approval of the Company (but without the need for approval by any other
party to this Agreement), become parties to this Agreement by executing and
delivering a counterpart signature page hereto, whereupon they shall be deemed
"Purchasers" for all purposes of this Agreement and any such Series C Preferred
Shares and Series C Warrants purchased pursuant to the Purchase Agreement shall
be deemed "Purchased Securities" hereunder.

            7.14 Permitted Transfers. Notwithstanding the restrictions on
transfer contained in Sections 2 and 5 herein, (i) Affiliates of Credit Suisse
First Boston Private Equity may transfer up to 5,000 Series C Preferred Shares
to Dr. Allan Greene (provided that at the time of such transfer he is an
accredited investor as defined in the rules promulgated under the Securities
Act) and (ii) any Purchaser may Transfer any Preferred Shares (and the rights
and obligations under this Agreement appurtenant to such Preferred Shares) to
any Affiliate that is an accredited investor as defined in the rules promulgated
under the Securities Act, so long as (a) such Purchaser gives prior written
notice of such Transfer to the Company, (b) the transferee, as a condition
precedent to such Transfer, delivers a written instrument to the Company (in
form and substance reasonably satisfactory to the Company) by which such
transferee agrees to be bound by the obligations imposed under this Agreement,
(c) such Purchaser, as a condition precedent to such Transfer, delivers to the
Company duly executed stock transfer powers or other transfer documentation (in
form and substance reasonable satisfactory to the Company); and (d) if so
requested by the Company, such Purchaser, as a condition precedent to such
Transfer, delivers to the Company an opinion of legal counsel, reasonably
satisfactory to the Company to the effect that such Transfer is exempt from the
registration requirements of the Securities Act.

                               [Signatures follow]
<PAGE>
                                                                              34

            This Second Amended and Restated Stockholders' Agreement is hereby
executed as of the date first above written.

                              NOVIRIO PHARMACEUTICALS LIMITED

                              By: /s/ Jean-Pierre Sommadossi
                                  ------------------------------
                                  Name: Jean-Pierre Sommadossi
                                  Title: Chief Executive Officer

                              BB BIOVENTURES L.P.

                              By: BAB BIOVENTURES L.P., its General Partner

                              By: BAB BIOVENTURES, N.V., its General Partner

                              By: /s/ Ansbert Gadicke
                                  -------------------------
                                  Name:  Ansbert Gadicke
                                  Title:  Managing Director

                              MPM ASSET MANAGEMENT INVESTORS 1998 LLC

                              By: /s/ Ansbert Gadicke
                                  -------------------------
                                  Name:  Ansbert Gadicke
                                  Title: Manager

                              MPM BIOVENTURES PARALLEL FUND, L.P.

                              By:  MPM Asset Management LLC, its General Partner

                              By: /s/ Ansbert Gadicke
                                  -------------------------
                                  Name:  Ansbert Gadicke
                                 Title: Manager

<PAGE>
                                                                              35

                              TVM MEDICAL VENTURES
                                  GMBH & CO. KG

                              By: /s/ Helmut Schuhsler
                                  --------------------------------
                                  Name: Helmut Schuhsler
                                  Title: Managing Partner

                              KB LUX VENTURE CAPITAL FUND-
                                  BIOTECHNOLOGY

                              By: /s/ John J. DiBello
                                  --------------------------------
                                  Name: John J. DiBello
                                  Title: Managing Partner

                              CLOPPENBURG AUTOMOBILE AG

                              By:_________________________________
                                  Name:
                                  Title:

                              CLOPPENBURG IMMOBIL AG

                              By:_________________________________
                                  Name:
                                  Title:

                              NOMURA INTERNATIONAL PLC

                              By: /s/ [ILLEGIBLE]
                                  --------------------------------
                                  Name:  [ILLEGIBLE]
                                  Title: Managing Director

                              ------------------------------------
                              Peter Merz

                              ------------------------------------
                              Robert Flammang

                              /s/ Jean-Pierre Sommadossi
                              ------------------------------------
                              Jean-Pierre Sommadossi

                              /s/ Raymond F. Schinazi
                              ------------------------------------
                              Raymond F. Schinazi

                              /s/ Bruno Lucidi
                              ------------------------------------
                              Bruno Lucidi
<PAGE>
                                                                              36

                               /s/ Chung K. Chu
                              ------------------------------------
                              Chung K. Chu

                               /s/ David Carder
                              ------------------------------------
                              David Carder

                               /s/ Jean-Louis Imbach
                              ------------------------------------
                              Jean-Louis Imbach

                               /s/ Gilles Gosselin
                              ------------------------------------
                              Gilles Gosselin

                               /s/ Robert Murphy
                              ------------------------------------
                              Robert Murphy

                              MPM ASSET MANAGEMENT LLC

                              By:_________________________________
                                  Name:  Ansbert Gadicke
                                  Title: Manager

                               /s/ Paolo La Colla
                              ------------------------------------
                              Paolo La Colla

                              ------------------------------------
                              Marc Blanchard

                              ------------------------------------
                              Xiao-Jian Zhou

                              ------------------------------------
                              Terri L. Hicks

                              ------------------------------------
                              Meng Yu Xie

                              ------------------------------------
                               Erika Cretton-Scott

                               /s/ Abdesslem Faraj
                              ------------------------------------
                                 Abdesslem Faraj

                               /s/ Christian Perigaud
                              ------------------------------------
                               Christian Perigaud
<PAGE>
                                                                              37

                              CREDIT SUISSE FIRST BOSTON EQUITY PARTNERS, L.P.

                              By:  Hemisphere Private Equity Partners, Ltd., its
                                   General Partner

                                   /s/ Ken Lohsen
                              By:__________________________________
                              Name:
                              Title:
                              Address: c/o CSFB Advisory Partners, L.L.C.
                                       11 Madison Avenue
                                       New York, NY 10010
                                       Attn:  Ken Lohsen
                                       Fax:  212.325.7887

                              CREDIT SUISSE FIRST BOSTON EQUITY PARTNERS
                              (BERMUDA), L.P.

                              By:  Hemisphere Private Equity Partners, Ltd., its
                                   General Partner

                                   /s/ Ken Lohsen
                              By:__________________________________
                              Name:
                              Title:
                              Address: c/o CSFB Advisory Partners, L.L.C.
                                       11 Madison Avenue
                                       New York, NY 10010
                                       Attn:  Ken Lohsen
                                       Fax:  212.325.7887
<PAGE>
                                                                              38

                              EMA PARTNERS FUND 2000, L.P.

                              By:  Credit Suisse First Boston (Bermuda) Limited,
                                   its General Partner

                              By:  /s/ Ken Lohsen
                                 __________________________________
                              Name:
                              Title:
                              Address: c/o CSFB Advisory Partners, L.L.C.
                                       11 Madison Avenue
                                       New York, NY 10010
                                       Attn:  Ken Lohsen
                                       Fax:  212.325.7887

                              EMA PRIVATE EQUITY FUND 2000, L.P.

                              By:  Credit Suisse First Boston (Bermuda) Limited,
                                   its General Partner

                              By:  /s/ Ken Lohsen
                                 __________________________________
                              Name:
                              Title:
                              Address: c/o CSFB Advisory Partners, L.L.C.
                                       11 Madison Avenue
                                       New York, NY 10010
                                       Attn:  Ken Lohsen
                                       Fax:  212.325.7887
<PAGE>
                                                                              39

                              CREDIT SUISSE FIRST BOSTON U.S. EXECUTIVE
                              ADVISORS, L.P.

                              By:  Hemisphere Private Equity Partners, Ltd., its
                                 General Partner

                              By:  /s/ Ken Lohsen
                                 __________________________________
                              Name:
                              Title:
                              Address: c/o CSFB Advisory Partners, L.L.C.
                                       11 Madison Avenue
                                       New York, NY 10010
                                       Attn:  Ken Lohsen
                                       Fax:  212.325.7887

                              HANSEATIC AMERICAS LDC

                              By: Hanseatic Partners LLC

                              By: Hanseatic Corporation

                              By: /s/ Paul Biddelman
                                 ________________________________

                                        Paul Biddelman
                                  Name: ___________________________

                                           President
                                  Title:  ____________________________

                              NOVARTIS BIOVENTURE FUND/NOVARTIS INTERNATIONAL AG

                              By: /s/ Peter Bissinger An Karabelas
                                  _________________________________

                                  Name: Peter Bissinger An Karabelas
                                        ___________________________
                                  Title: __________________________

                              BIOMEDICAL SCIENCES INVESTMENT FUND PTE LTD.

                              By: /s/ Lily Chan
                                  ________________________________

                                  Name: Lily Chan
                                        __________________________

                                  Title: General Manager
                                         _________________________
<PAGE>
                                                                              40

                              ADROIT PRIVATE EQUITY AG

                              By: /s/ Alexander Pfeifer
                                  ________________________________
                                  Name: Alexander Pfeifer
                                        ___________________________

                                  Title: Partner
                                         ____________________________

                              By: /s/ Andrea Gambazzi
                                  ________________________________

                                  Name: Andrea Gambazzi
                                        ___________________________

                                  Title: Partner
                                         ____________________________

                              BANK AMERICA INVESTMENT CORPORATION

                              By: /s/ Jeffrey G. Berry
                                  ________________________________

                                  Name: Jeffrey G. Berry
                                        ___________________________

                                  Title: Managing Director
                                         ____________________________

                              SWAN PRIVATE EQUITY VERWALTUNGS GMBH

                              By: /s/ Markus Voelkel
                                  ________________________________

                                  Name: Markus Voelkel
                                        ___________________________

                                  Title: Managing Director
                                         ____________________________
<PAGE>
                                   SCHEDULE A

<TABLE>
<CAPTION>
                                     NUMBER              NUMBER OF            NUMBER OF            NUMBER OF          NUMBER OF
                                  OF ORDINARY             SERIES A             SERIES B             SERIES C           SERIES C
       SECURITY HOLDER               SHARES           PREFERRED SHARES     PREFERRED SHARES     PREFERRED SHARES       WARRANTS
----------------------------------------------------------------------------------------------------------------------------------
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
PURCHASERS:                               --            10,985,331             773,600               694,142            416,485

BB BioVentures L.P.
One Cambridge Center
9th Floor
Cambridge, MA  02142
Telephone:  617-225-2360
Telecopy:  617-225-0036
----------------------------------------------------------------------------------------------------------------------------------
MPM BioVentures Parallel                  --               865,591             105,067               104,646            62,788
Fund, L.P.
One Cambridge Center
9th Floor
Cambridge, MA  02142
Telephone:  617-225-2360
Telecopy:  617-225-0036
----------------------------------------------------------------------------------------------------------------------------------
MPM Asset Management                      --               137,871              10,222                 9,293              5,576
Investors 1998 LLC
One Cambridge Center
9th Floor
Cambridge, MA  02142
Telephone:  617-225-2360
Telecopy:  617-225-0036
----------------------------------------------------------------------------------------------------------------------------------
TVM Medical Ventures                      --                    --           1,777,778
GmbH & Co. KG
Maximilianstr. 35
80539 Munchen, Germany
Telephone:  4989 9989 9222
Telecopy:  4989 9989 9255
----------------------------------------------------------------------------------------------------------------------------------
KB Lux Venture Capital                    --                    --             666,667
  Fund-Biotechnology
43 Blvd. Royal
L-2955 Luxembourg
Telephone:  352 4681  94577
Telecopy:  352 4797 73230
Attn:  Mr. Patrick Vander
Eecken
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
                                     NUMBER              NUMBER OF            NUMBER OF            NUMBER OF          NUMBER OF
                                  OF ORDINARY             SERIES A             SERIES B             SERIES C           SERIES C
       SECURITY HOLDER               SHARES           PREFERRED SHARES     PREFERRED SHARES     PREFERRED SHARES       WARRANTS
----------------------------------------------------------------------------------------------------------------------------------
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
CLOPPENBURG AUTOMOBIL - AG                --                    --             111,111
Chamissostrasse 12
D-40237 Dusseldorf,
Germany
Attn: Mr. Jorn
Cloppenburg
Telephone: 4921 191 2940
Telecopy: 4921 1912 9420
----------------------------------------------------------------------------------------------------------------------------------
CLOPPENBURG IMMOBIL - AG                  --                    --              66,667
Chamissostrasse 12
D-40237 Dusseldorf,
Germany
Attn:  Mr. Jorn
Cloppenburg
Telephone: 4921 191 2940
Telecopy: 4921 1912 9420
----------------------------------------------------------------------------------------------------------------------------------
Peter Merz                                --                    --              44,444
Froriep Renggli
Bellerivestr. 201
CH-8034 Zurich,
Switzerland
Telephone: 41 1386 6000
Telecopy: 41 1383 6050
----------------------------------------------------------------------------------------------------------------------------------
Nomura International plc                  --                    --           1,777,778               808,081            484,848
Nomura House
1, St. Martin's Le-Grand
London, England
Attn:  Denise Pollard-Knight
Telephone:  44 171 521 3231
Telecopy:  33 171 521 3699
----------------------------------------------------------------------------------------------------------------------------------
Robert Flammang                           --                    --             222,222
7 Rue Suffren-Reymond
Monaco  908000
Telephone:  377-93-302-304
Telecopy:  377-93-15-98-44
----------------------------------------------------------------------------------------------------------------------------------
Credit Suisse First Boston
  Equity Partners, L.P.                   --                    --                  --             1,666,127            999,676
c/o CSFB Advisory Partners,
L.L.C.
11 Madison Avenue
New York, NY 10010
Attn:  Ken Lohsen
Fax:  212.325.7887
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>

                                       2
<PAGE>
<TABLE>
<CAPTION>
                                     NUMBER              NUMBER OF            NUMBER OF            NUMBER OF          NUMBER OF
                                  OF ORDINARY             SERIES A             SERIES B             SERIES C           SERIES C
       SECURITY HOLDER               SHARES           PREFERRED SHARES     PREFERRED SHARES     PREFERRED SHARES       WARRANTS
----------------------------------------------------------------------------------------------------------------------------------
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
Credit Suisse First Boston
  Equity Partners (BERMUDA),              --                    --                  --               465,725            279,435
  L.P.
c/o CSFB Advisory Partners,
L.L.C.
11 Madison Avenue
New York, NY 10010
Attn:  Ken Lohsen
Fax:  212.325.7887
----------------------------------------------------------------------------------------------------------------------------------
EMA Partners Fund 2000, L.P.
c/o CSFB Advisory Partners,               --                    --                  --               125,091             75,055
  L.L.C.
11 Madison Avenue
New York, NY 10010
Attn:  Ken Lohsen
Fax:  212.325.7887
----------------------------------------------------------------------------------------------------------------------------------
EMA Private Equity Fund 2000,
  L.P.                                    --                    --                  --               165,818             99,491
c/o CSFB Advisory Partners,
  L.L.C.
11 Madison Avenue
New York, NY 10010
Attn:  Ken Lohsen
Fax:  212.325.7887
----------------------------------------------------------------------------------------------------------------------------------
Credit Suisse First Boston
  U.S. Executive Advisors,                --                    --                  --                 1,482                889
  L.P.
c/o CSFB Advisory Partners,
L.L.C.
11 Madison Avenue
New York, NY 10010
Attn:  Ken Lohsen
Fax:  212.325.7887
----------------------------------------------------------------------------------------------------------------------------------
Hanseatic Americas LDC                    --                    --                  --               707,071            424,242
----------------------------------------------------------------------------------------------------------------------------------
Novartis Bioventure
  Fund/Novartis International             --                    --                  --             1,010,101            606,061
  AG
----------------------------------------------------------------------------------------------------------------------------------
Biomedical Sciences
  Investment Fund Pte Ltd.                --                    --                  --               606,061            363,636
----------------------------------------------------------------------------------------------------------------------------------
Adroit Private Equity AG                  --                    --                  --               606,061            363,636
----------------------------------------------------------------------------------------------------------------------------------
Bank America Investment
  Corporation                             --                    --                  --               404,040            242,424
----------------------------------------------------------------------------------------------------------------------------------
Swan Private Equity
  Verwaltungs GmbH                        --                    --                  --               303,030            181,818
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>

                                       3
<PAGE>
<TABLE>
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
----------------------------------------------------------------------------------------------------------------------------------
STOCKHOLDERS:                        600,000                    --                  --                    --

Jean-Louis Imbach
91 Impasse Des Lucques
3400 Montpellier, France
Telephone and Telecopy:
  011-33-04-6763-0043
----------------------------------------------------------------------------------------------------------------------------------
Gilles Gosselin                      600,000                    --                  --                    --
Residence "Lanc des
Azceaux"
Bariment F1.83 rue Calvin
400 Avenue Saul Rimbaund
34080 Montpellier, France
Telephone:
011-33-04-6754-7793
----------------------------------------------------------------------------------------------------------------------------------
Jean-Pierre Sommadossi             3,000,000               100,000                  --                    --
5075 Greystone Way
Birmingham, AL 35242
Telephone: 205-995-8888
----------------------------------------------------------------------------------------------------------------------------------
Raymond F. Schinazi                1,125,000               100,000                  --                    --
1524 Regency Walk Drive
Decatur, GA  30033
Telephone:  404-320-9209
Telecopy:  404-728-7726
----------------------------------------------------------------------------------------------------------------------------------
Bruno Lucidi                         600,000               100,000                  --                    --
4, Allec La Croix de Jardins
78740 Vaux La Leine
France
Telephone and Telecopy:
  011-33-134-80-6461
----------------------------------------------------------------------------------------------------------------------------------
Chung K. Chu                         75,000                 50,000                  --                    --
115 Cedar Springs Place
Athens, GA  30605
Telephone:  706-549-3867
Telecopy:  706-542-5381
----------------------------------------------------------------------------------------------------------------------------------
David Carder                         15,000                 50,000                  --                    --
4208 Antietam Drive
Birmingham, AL  35213
Telephone:  205-870-5223
Telecopy:  205-877-3311
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>

                                       4
<PAGE>
<TABLE>
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
----------------------------------------------------------------------------------------------------------------------------------
Robert Murphy                        187,500                25,000                  --                    --
2202 North Cleveland Street
Chicago, IL  60614
Telephone:  312-908-0949
Telecopy:  312-908-8281
----------------------------------------------------------------------------------------------------------------------------------
MPM Asset Management LLCBB           206,897                    --                  --                    --
BioVentures L.P.
One Cambridge Center
9th Floor
Cambridge, MA  02142
Telephone:  617-225-2360
Telecopy:  617-225-0036
----------------------------------------------------------------------------------------------------------------------------------
Paolo La Colla                       187,500                    --                  --                    --
Poggio dei Pini
V strada n.11
09012 Capoterra (Ca)
Italy
Telephone:  011-070-670-989
Telecopy:  011-070-670-802
----------------------------------------------------------------------------------------------------------------------------------
Marc Blanchard                       20,000                     --                  --                    --
12, Rue Littre
75006, Paris, France
Telephone:
011-33-01-42-12-7111
Telecopy:
011-33-01-42-12-7110
----------------------------------------------------------------------------------------------------------------------------------
Xiao-Jian Zhou                       12,000                     --                  --                    --
4705 Wooddale Lane
Pelham, AL  35124
Telephone:  205-403-0738
Telecopy:  205-975-4871
----------------------------------------------------------------------------------------------------------------------------------
Terri L. Hicks                      12,000                     --                  --                    --
5228 Bonnie Ruth Road
Trussville, AL  35173
Telephone:  205-655-2610
Telecopy:  205-975-4871
----------------------------------------------------------------------------------------------------------------------------------
Meng Yu Xie                        12,000                     --                  --                    --
1324 11th Avenue South-B6
Birmingham, AL  35205
Telephone:  205-918-0382
Telecopy:  205-975-4871
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>

                                       5
<PAGE>
<TABLE>
<S>                              <C>                  <C>                  <C>                  <C>                  <C>
----------------------------------------------------------------------------------------------------------------------------------
Erika Cretton-Scott                  12,000                     --                  --                    --
P.O. Box 705
Jemison, AL  35085
Telephone:  205-688-4100
Telecopy:  205-975-4871
----------------------------------------------------------------------------------------------------------------------------------
Abdesslem Faraj                      12,000                     --                  --                    --
1142 Alford Avenue
Hoover, AL 35226
Telephone:  205-979-4380
Telecopy:  205-975-4871
----------------------------------------------------------------------------------------------------------------------------------
Christian Perigaud                   12,000                     --                  --                    --
121 rue du Comtat Venaissin
34080 Montpellier, France
Telephone: 011-33-04-6745-0266
----------------------------------------------------------------------------------------------------------------------------------
</TABLE>

                                       6
<PAGE>
                                    EXHIBIT 1

                               STOCKHOLDER JOINDER

            By execution of this Stockholder Joinder, the undersigned agrees to
become a party to that certain Second Amended and Restated Stockholders'
Agreement dated as of April 24, 2001, among Novirio Pharmaceuticals Limited, a
Cayman Islands corporation, and certain of its stockholders. The undersigned
shall have all the rights, and shall observe all the obligations, applicable to
a Stockholder:

Name:__________________________

Address for Notices:

_______________________________
_______________________________
_______________________________
_______________________________

                                            Signature:________________________

Date:__________________________

<PAGE>

                                  Amendment to
               Second Amended and Restated Stockholders' Agreement

                             Approved April 11, 2002

The following provisions of the Stockholders' Agreement have been amended as
follows:

         (i)      The introductory paragraph of the Stockholders' Agreement
                  shall be amended and restated in its entirety as follows:

                  "THIS SECOND AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT (the
                  "Agreement") is entered into as of April 24, 2001, by and
                  among NOVIRIO PHARMACEUTICALS LIMITED, a corporation formed
                  under the laws of the Cayman Islands (together with any
                  continuing corporation or successor in interest resulting
                  from, including without limitation, the consummation of a
                  Reorganization Event (as defined below), the "Company"), the
                  Purchasers (as defined herein) and the Stockholders (as
                  defined herein)."

         (ii)     Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Charter" in its entirety and
                  inserting the following definition in lieu thereof:

                  "`Charter' means the articles of association, articles of
                  incorporation, certificate of incorporation or other
                  organizational document(s) of the Company, as applicable and
                  as may be in effect from time to time."

         (iii)    Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Equity Incentive Plan" in its
                  entirety and inserting the following definition in lieu
                  thereof:

                  "`Equity Incentive Plan' means the 1998 Equity Incentive Plan
                  of the Company pursuant to which Ordinary Shares or other
                  securities to acquire such Ordinary Shares may be issued to
                  employees, officers, directors, consultants and advisors of
                  the Company or its majority owned subsidiaries."

         (iv)     Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Family Member" in its entirety and
                  inserting the following definition in lieu thereof:

                  "`Family Member' shall mean, as to any Person, (i) such
                  Person's spouse, child (including a stepchild or an adopted
                  child), or grandchild or a trust for the exclusive benefit of
                  such Person and/or such Person's spouse, child (including a
                  stepchild or an adopted child), or grandchild or (ii) a
                  corporation, limited liability company, partnership, limited
                  partnership, limited liability partnership or other similar
                  entity, the beneficial owners of which consist exclusively of
                  such Person and/or such Person's spouse, child (including a
                  stepchild or an adopted child) and/or grandchild."

         (v)      Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Ordinary Shares" in its entirety
                  and inserting the following definition in lieu thereof:

                  "`Ordinary Shares' means the Ordinary Shares, $.001 par value
                  per share, of the Company, or such shares of Common Stock,
                  $.001 par value per share, of the Company which (i) Ordinary
                  Shares may be converted into or substituted or exchanged for,
                  or (ii) after a Reorganization Event, would otherwise
                  represent such Ordinary Shares; in each case, in connection
                  with or pursuant to a Reorganization Event. For purposes of
                  calculating the Stockholders' relative holdings of the
                  Ordinary Shares, including without limitation for purposes of
                  Sections 4.1(c) and 5.2(b) hereof, all Preferred Shares of the
                  Company shall be deemed to have been converted into Ordinary
                  Shares."

         (vi)     Section 1.1 entitled "Definitions" shall be amended by adding
                  the following definition:

                  "Reorganization Event" means the consummation of any merger,
                  consolidation, reorganization, recapitalization, statutory
                  share exchange, reincorporation, deregistration and/or
                  domestication involving the Company and, as a result of such
                  transaction, all of
<PAGE>
                  the individuals and entities who were the beneficial owners of
                  the then outstanding capital stock and/or share capital of the
                  Company, as applicable, prior to the Reorganization Event
                  beneficially own, directly or indirectly, in the same
                  proportion, all of the outstanding capital stock and/or share
                  capital of the resulting, succeeding or continuing
                  corporation."

         (vii)    Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Series A Preferred Shares" in its
                  entirety and inserting the following definition in lieu
                  thereof:

                  "`Series A Preferred Shares' shall mean the Series A
                  Convertible Preferred Shares, $.001 par value per share, of
                  the Company or such series of Preferred Stock, $.001 par value
                  per share, of the Company (i) which Series A Preferred Shares
                  may be converted into, or substituted or exchanged for, or
                  (ii) after a Reorganization Event, would otherwise represent
                  such Series A Convertible Preferred Shares; in each case, in
                  connection with or pursuant to a Reorganization Event."

         (viii)   Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Series B Preferred Shares" in its
                  entirety and inserting the following definition in lieu
                  thereof:

                  "`Series B Preferred Shares' shall mean the Series B
                  Convertible Preferred Shares, $.001 par value per share, of
                  the Company or such series of Preferred Stock, $.001 par value
                  per share, of the Company (i) which Series B Preferred Shares
                  may be converted into, or substituted or exchanged for, or
                  (ii) after a Reorganization Event, would otherwise represent
                  such Series B Convertible Preferred Shares; in each case, in
                  connection with or pursuant to a Reorganization Event."

         (ix)     Section 1.1 entitled "Definitions" shall be amended by
                  deleting the definition of "Series C Preferred Shares" in its
                  entirety and inserting the following definition in lieu
                  thereof:

                  "`Series C Preferred Shares' shall mean the Series C
                  Convertible Preferred Shares, $.001 par value per share, of
                  the Company or such series of Preferred Stock, $.001 par value
                  per share, of the Company (i) which Series C Preferred Shares
                  may be converted into, or substituted or exchanged for, or
                  (ii) after a Reorganization Event, would otherwise represent
                  such Series C Convertible Preferred Shares; in each case, in
                  connection with or pursuant to a Reorganization Event."

         (x)      Section 2.1(a)(A) of the Stockholders' Agreement shall be
                  amended by deleting the text thereof in its entirety and
                  inserting the following text in lieu thereof:

                  "Within one hundred eighty (180) days immediately following
                  the effective date of any registration statement on the
                  Commission's Form S-1 (or any successor form to Form S-1)
                  pertaining to an underwritten offering of securities of the
                  Company part or all of which was for its own account unless
                  otherwise consented to by the underwriter of such offering;
                  or"

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