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                                                                   EXHIBIT 10.16

               FOURTH AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT

     THIS FOURTH AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT, dated this 22nd
day of May 2001, is entered into by and among NITROMED, INC., a Delaware
corporation (the "Corporation"), those Stockholders of the Corporation listed on
SCHEDULE 1 hereto (hereinafter referred to collectively as the "Investors"),
those individuals listed on SCHEDULE 2 hereto (the "Management Holders"), and
The Brigham and Women's Hospital, Inc. ("BWH"). It is expressly agreed among the
parties that (i) BWH shall have no rights, liabilities or responsibilities
whatsoever under Sections 2.2, 2.4 through 2.14, 3.1 through 3.4, 3.6 and 5.1
through 5.5 hereof and (ii) the Management Holders shall have no rights,
liabilities or responsibilities whatsoever under Sections 2, 3.1 through 3.4,
3.6 and 5 hereof.

                              W I T N E S S E T H:

     WHEREAS, The Corporation has previously entered into a Third Amended and
Restated Stockholders' Agreement dated as of May 17, 1999, as amended from time
to time, (the "Old Stockholders' Agreement") with holders of the Corporation's
Series A Convertible Preferred Stock (the "Series A Investors"), holders of the
Corporation's Series B Convertible Preferred Stock (the "Series B Investors"),
holders of the Corporation's Series C Convertible Preferred Stock (the "Series C
Investors"), holders of the Corporation's Series D Convertible Preferred Stock
(the "Series D Investors"), the individuals listed on Schedule 2 thereto and,
with respect to certain provisions, BWH; and

     WHEREAS, the Corporation has authorized a new series of Preferred Stock to
be designated "Series E Convertible Preferred Stock," par value $.01 per share
("Series E Preferred Stock"); and

     WHEREAS, the Corporation is entering into a Series E Convertible Preferred
Stock Purchase Agreement dated the date hereof in connection with which the
Corporation has agreed to sell shares of its Series E Preferred Stock to certain
investors (the "Series E Investors"), and the Corporation desires to grant to
the Series E Investors certain registration, preemptive and other rights with
respect to such Series E Preferred Stock; and

     WHEREAS, the Corporation, the Series A Investors, the Series B Investors,
the Series C Investors, the Series D Investors, the Management Holders and BWH
believe it to be in their mutual best interests that the Old Stockholders'
Agreement be amended and restated in its entirety in order to accommodate the
creation of the Series E Preferred Stock and the rights to be granted to the
Series E Investors.

     NOW, THEREFORE, in consideration of the foregoing and of the respective
covenants and undertakings of the Corporation and the Investors hereunder, the
parties hereto do hereby agree as follows:

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     SECTION 1. DEFINITIONS. As used herein, the following terms shall have the
following respective meanings:

     BOARD shall mean the Board of Directors of the Corporation.

     BUDGET shall have the meaning set forth in Section 2.8 hereof.

     BU WARRANT shall mean collectively (i) the Series B Preferred Stock
Purchase Warrant, to purchase 412,500 Series B Preferred Shares, issued on April
11, 1996 by the Corporation to Trustees of Boston University; (ii) the Series B
Preferred Stock Purchase Warrant, to purchase 41,250 Series B Preferred Shares,
issued on September 30, 1996 by the Corporation to Trustees of Boston
University; and (iii) the Series B Preferred Stock Purchase Warrant, to purchase
41,250 Series B Preferred Shares, issued on April 7, 1997 by the Corporation to
Trustees of Boston University.

     BWH shall mean The Brigham and Women's Hospital, Inc.

     BWH SECURITIES shall have the meaning set forth in Section 2.3(a) hereof.

     CERTIFICATE shall mean the Fifth Restated Certificate of Incorporation of
the Corporation.

     COMMISSION shall mean the U.S. Securities and Exchange Commission.

     COMMON STOCK shall mean the Common Stock, par value $.01 per share, of the
Corporation.

     ENVIRONMENTAL LAWS shall mean all applicable federal, state, foreign and
local laws, ordinances, rules and regulations that regulate, fix liability for,
or otherwise relate to, the handling, use (including use in industrial
processes, in construction, as building materials, or otherwise), storage and
disposal of hazardous and toxic wastes and substances, and to the discharge,
leakage, presence, migration, threatened release or release (whether by
disposal, a discharge into any water source or system or into the air, or
otherwise) of any pollutant or effluent or otherwise related to pollution or the
protection of human health, the environment or wildlife. Without limiting the
preceding sentence, the term "Environmental Laws" shall specifically include the
following federal and state laws, as amended:

                                     FEDERAL

               Comprehensive Environmental Response,
               Compensation and Liability Act of 1980, 42 U.S.C.
               9601 ET SEQ.;

               Resource Conservation and Recovery Act of 1976,
               42 U.S.C. 6901 ET SEQ.;

               Federal Water Pollution Control Act, 33 U.S.C.
               1251 ET SEQ.; and

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               Clean Air Act, 42 U.S.C. 7401 ET SEQ.

                                      STATE

                      MASSACHUSETTS ENVIRONMENTAL STATUTES

               Massachusetts Clean Waters Act, Mass. Gen. L.
               Ch. 21, Section 26, ET SEQ., and regulations
               thereto;

               Massachusetts Solid Waste Disposal Laws, Mass.
               Gen. L. Ch. 16, Section 18, ET SEQ., and Ch. 111,
               Section 105A, and regulations thereto;

               Massachusetts Oil and Hazardous Materials Release
               Prevention and Response Act, Mass. Gen. L., Ch.
               21E, Section 1, ET SEQ., and regulations thereto;

               Massachusetts Solid Waste Facilities Law, Mass.
               Gen. L., Ch. 21H, Section 1, ET SEQ., and
               regulations thereto;

               Massachusetts Toxic Use Reduction Act, Mass.
               Gen. L., Ch. 211, Section 1, ET SEQ., and
               regulations thereto;

               Massachusetts Litter Control Laws, Mass. Gen. L.
               Ch. 111, Section 150A, ET SEQ., and regulations
               thereto;

               Massachusetts Wetlands Protection Laws, Mass.
               Gen. L., Ch. 130, Section 105, ET SEQ., and
               regulations thereto;

               Massachusetts Environmental Air Pollution Control
               Law, Mass. Gen. L., Ch. 101, Section 2B, ET SEQ.,
               and regulations thereto;

               Massachusetts Environmental Policy Act, Mass.
               Gen. L. 30, Section 61, ET SEQ., and regulations
               thereto; and

               Massachusetts Hazardous Waste Laws, Mass. Gen. L.
               Ch. 21C, Section 1, ET SEQ., and regulations
               thereto.

     EQUITY PERCENTAGE shall mean, as to any Investor, that percentage figure
which expresses the ratio that (a) the number of shares of issued and
outstanding Common Stock then owned by such Investor bears to (b) the aggregate
number of shares of issued and outstanding Common

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Stock then owned by all Investors. For purposes solely of the computation set
forth in clauses (a) and (b) above, all issued and outstanding securities held
by the Investors that are convertible into or exercisable or exchangeable for
shares of Common Stock (including any issued and issuable shares of Preferred
Stock) or for any such convertible, exercisable or exchangeable securities,
shall be treated as having been so converted, exercised or exchanged at the rate
or price at which such securities are convertible, exercisable or exchangeable
for shares of Common Stock in effect at the time in question (which, for
purposes of Section 2.3 of this Agreement, shall be at the time of delivery by
the Corporation of the notice of the Offer contemplated by Section 2.3(b)),
whether or not such securities are at such time immediately convertible,
exercisable or exchangeable.

     EQUITY PERCENTAGE SECURITIES shall have the meaning set forth in Section
2.3(a) hereof.

     EXCHANGE ACT shall mean the Securities Exchange Act of 1934, as amended.

     EXCHANGE ACT REGISTRATION STATEMENT shall have the meaning set forth in
Section 2.5 hereof.

     EXCESS SECURITIES shall have the meaning set forth in Section 2.3(d)
hereof.

     EXCESS SECURITIES NOTICE shall have the meaning set forth in Section 2.3(d)
hereof.

     EXCESS SECURITIES PERIOD shall have the meaning set forth in Section 2.3(d)
hereof.

     EXCLUDED FORMS shall have the meaning given such term in Section 3.5
hereof.

     EXCLUDED SECURITIES shall mean, collectively:

          (i)   the Reserved Shares;

          (ii)  Common Stock issued or issuable to officers, directors or
employees of or consultants or independent contractors to the Corporation,
pursuant to any written agreement, plan or arrangement, including pursuant to
any options granted under the 1993 Equity Incentive Plan of the Corporation (the
"1993 Equity Incentive Plan"), to purchase, or rights to subscribe for, such
Common Stock, that is set forth on Schedule 5.2 of the Series E Stock Purchase
Agreement or that has been approved in form and in substance by the holders of a
majority of the combined voting power of the Series Preferred Shares then
outstanding, calculated in accordance with Section A.6(a) of Article III of the
Certificate (including, in such calculation, any outstanding Restricted Shares
held by such holders), and which, as a condition precedent to the issuance of
such shares, provides for the vesting of such shares and subjects such shares to
restrictions on transfers and rights of first offer in favor of the Corporation
that have been approved by the holders of a majority of the combined voting
power of the Series Preferred Shares then outstanding, calculated in accordance
with Section A.6(a) of Article III of the Certificate (including, in such
calculation, any outstanding Restricted Shares held by such holders),
(collectively, the "Required Terms"), unless any of such Required Terms are
waived by holders at least a majority of the voting power of the Series
Preferred Shares then outstanding (determined as set forth in Section A.6(a) of
the Certificate); PROVIDED, HOWEVER, that the

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maximum number of shares of Common Stock hereafter issuable pursuant to the 1993
Equity Incentive Plan and all such agreements, plans and arrangements shall not
exceed 2,288,200 shares (subject to adjustment as required to comply with any
anti-dilution rights set forth in any such agreement, plan or arrangement);

          (iii) Common Stock issued as a stock dividend payable in shares of
Common Stock, or capital stock of any class issuable upon any subdivision,
recombination, split-up or reverse stock split of all the outstanding shares of
such class of capital stock of the Corporation;

          (iv)  any securities issued pursuant to the acquisition by the
Corporation of any other corporation, partnership, joint venture, trust or other
entity by any merger, stock acquisition, reorganization, purchase of
substantially all assets or otherwise in which the Corporation, or its
stockholders of record immediately prior to the effective date of such
transaction, directly or indirectly, own at least a majority of the voting power
of the acquired entity or the resulting entity after such transaction; and

          (v)   any shares of Common Stock, Preferred Stock or any other
security convertible into or exercisable or exchangeable for Common Stock or
Preferred Stock issued to banks or leasing companies in order to obtain
financing or to secure leases of equipment; and

          (vi)  a maximum of 516,364 shares of Common Stock (subject to
adjustment) issued or issuable upon the exercise of the 1994 Bridge Warrants,
1995 Bridge Warrants, 1996 Bridge Warrants and the 1994 Capital Support
Warrants;

     GROUP shall mean: (i) as to an Investor that is a limited partnership: (A)
any and all of the venture capital limited partnerships now existing or
hereafter formed that are affiliated with or under common control with one or
more of the general partners or one or more general partners of the general
partner of such Investor and any predecessor or successor thereto, (B) any
limited partner of such Investor, and (C) in the case of an HCV Fund, the HCV
Group; (ii) as to any Investor that is a trust, any grantor or beneficiary
thereof, or any other trust, corporate entity or partnership under common
control with such trust; and (iii) as to any Investor, any other Investor.

     HAZARDOUS MATERIALS shall include without limitation, any flammable
explosives, petroleum products, petroleum byproducts, radioactive materials,
hazardous wastes, hazardous substances, toxic substances or other similar
materials regulated by Environmental Laws.

     HCV FUND shall mean any of HCV I, HCV II, HCV III, HCV IV, HCV V or HCV VI.

     HCV GROUP shall mean, collectively, (i) any HCV Fund, (ii) any venture
capital limited partnership now existing or hereafter formed which is affiliated
with or under common control with one or more general partners of any general
partner of an HCV Fund; (iii) any limited partners or affiliates of an HCV Fund;
and (iv) any successors or assigns of any of the foregoing persons.

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     HCV I shall mean HealthCare Ventures I, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV I under this Agreement.

     HCV II shall mean HealthCare Ventures II, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV II under this Agreement.

     HCV III shall mean HealthCare Ventures III, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV III under this Agreement.

     HCV IV shall mean HealthCare Ventures IV, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV IV under this Agreement.

     HCV V shall mean HealthCare Ventures V, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV V under this Agreement.

     HCV VI shall mean HealthCare Ventures VI, L.P., a Delaware limited
partnership, including any successor thereto or any assignee of the interest, in
whole or in part, of HCV VI under this Agreement.

     INCENTIVE SHARES shall mean a maximum of 2,288,200 shares of Common Stock
duly reserved for issuance in connection with options available under the 1993
Equity Incentive Plan.

     INITIAL PUBLIC OFFERING shall mean a firm commitment underwritten public
offering of Common Stock of the Corporation registered under the Securities Act,
pursuant to which (a) Common Stock is offered to the public at a price of at
least $14.4074 per share (subject to adjustment to reflect stock splits, stock
dividends, stock combinations and like occurrences), and (b) the net proceeds to
the Corporation are at least $15,000,000.

     INVESTORS shall mean severally, but not jointly and severally (i) each of
the persons listed on Schedule 1 hereto and (ii) Trustees of Boston University
at such time as Trustees of Boston University shall have exercised the BU
Warrants and received shares of the Corporation's Series B Preferred Stock.

     MAJOR INVESTOR shall mean each Investor that holds at least 100,000 Series
Preferred Shares.

     MANAGEMENT HOLDERS shall mean the individuals listed on Schedule 2 hereto.

     NOTICE OF ACCEPTANCE shall have the meaning set forth in Section 2.3(c)
hereof.

     OFFER shall have the meaning set forth in Section 2.3(b) hereof.

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     OFFERED SECURITIES shall mean, except for Excluded Securities, (i) any
shares of Common Stock, Preferred Stock or any other equity security of the
Corporation, (ii) any debt security or capitalized lease with any equity feature
with respect to the Corporation, or (iii) any option, warrant or other right to
subscribe for, purchase or otherwise acquire any such equity security, debt
security or capitalized lease.

     OTHER SHARES shall have the meaning set forth in Section 3.5(e) hereof.

     PREFERRED STOCK shall mean the Preferred Stock, par value $.01 per share,
of the Corporation.

     PREFERRED STOCKHOLDERS shall mean, collectively, all holders of shares of
Preferred Stock of the Corporation.

     PROPERTY shall include, without limitation, land, buildings and laboratory
facilities owned or leased by the Corporation or as to which the Corporation now
has any duties, responsibilities (for clean-up, remedy or otherwise) or
liabilities under any Environmental Laws, or as to which the Corporation or any
subsidiary of the Corporation may have such duties, responsibilities or
liabilities because of past acts or omissions of the Corporation or any such
subsidiary or their predecessors, or because the Corporation or any such
subsidiary or their predecessors in the past was such an owner or operator of,
or bore some other relationship with, such land, buildings and/or laboratory
facilities.

     REFUSED SECURITIES shall have the meaning set forth in Section 2.3(f)
hereof.

     RESERVED SHARES shall collectively mean the shares of Common Stock reserved
by the Corporation for issuance upon the conversion of the Series Preferred
Shares or upon exercise of the Incentive Shares.

     RESTRICTED SECURITIES shall mean: (i) any of the Series Preferred Shares
and the Common Stock issued or issuable upon the conversion of the Series
Preferred Shares, all shares of Common Stock issued or issuable in respect
thereof by way of stock splits, stock dividends, stock combinations,
recapitalizations or like occurrences, and any other shares of Common Stock or
other securities of the Corporation which may be issued hereafter to any of the
Investors or any member of their Group which are convertible into or exercisable
or exchangeable for shares of Common Stock (including, without limitation, other
classes or series of Convertible Preferred Stock, warrants, options or other
rights to purchase Common Stock or convertible debentures or other convertible
debt Securities) and the Common Stock issued or issuable upon such conversion or
exercise of such other securities, which have not been sold (a) in connection
with an effective registration statement filed pursuant to the Securities Act,
or (b) pursuant to Rule 144 or Rule 144A promulgated by the Commission under the
Securities Act; and (ii) solely for the purpose of Sections 3.5, 3.7, 3.8, 3.9,
3.10 and 4 hereof, any shares of Common Stock issued to BWH or to the Management
Holders, and all shares of Common Stock issued or issuable in respect thereof by
way of stock splits, stock dividends, stock combinations, recapitalizations or
like occurrences, which have not been sold (a) in connection with an effective
registration

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statement filed pursuant to the Securities Act, or (b) pursuant to Rule 144 or
Rule 144A promulgated by the Commission under the Securities Act.

     RESTRICTED SHARES shall mean the shares of Common Stock issued or issuable
upon the conversion or exchange of the Restricted Securities or otherwise
constituting a portion of the Restricted Securities.

     SECURITIES ACT shall mean the Securities Act of 1933, as amended.

     SERIES A PREFERRED SHARES shall mean shares of Series A Preferred Stock
issued or issuable pursuant to the Series A Stock Purchase Agreement.

     SERIES A PREFERRED STOCK shall mean Series A Convertible Preferred Stock,
par value $.01 per share, of the Corporation.

     SERIES A STOCK PURCHASE AGREEMENT shall mean the Convertible Preferred
Stock Purchase Agreement, dated December 3, 1993, among the Corporation and the
Series A Investors listed on Schedule 1 thereto.

     SERIES B PREFERRED SHARES shall mean shares of Series B Preferred Stock
issued or issuable pursuant to (i) the Series B Stock Purchase Agreements and
(ii) the BU Warrant.

     SERIES B PREFERRED STOCK shall mean Series B Convertible Preferred Stock,
par value $.01 per share, of the Corporation.

     SERIES B STOCK PURCHASE AGREEMENTS shall mean (i) the Series B Convertible
Preferred Stock Purchase Agreement dated June 20, 1995 among the Corporation and
the Series B Investors listed on Schedule 1 thereto and (ii) the Series B
Convertible Preferred Stock Purchase Agreement dated April 4, 1997 between the
Corporation and the Series B Investors listed on Schedule 1 thereto.

     SERIES C PREFERRED SHARES shall mean shares of Series C Preferred Stock
issued or issuable pursuant to the Series C Stock Purchase Agreement.

     SERIES C PREFERRED STOCK shall mean Series C Convertible Preferred Stock,
par value $.01 per share, of the Corporation.

     SERIES C STOCK PURCHASE AGREEMENT shall mean the Series C Convertible
Preferred Stock Purchase Agreement, dated December 31, 1997, among the
Corporation and the Series C Investors listed on Schedule I thereto.

     SERIES D PREFERRED SHARES shall mean shares of Series D Preferred Stock
issued or issuable pursuant to the Series D Stock Purchase Agreement.

     SERIES D PREFERRED STOCK shall mean Series D Convertible Preferred Stock,
par value $.01 per share, of the Corporation.

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     SERIES D STOCK PURCHASE AGREEMENT shall mean the Series D Convertible
Preferred Stock Purchase Agreement, dated May 17, 1999, among the Corporation
and the Series D Investors listed on Schedule I thereto.

     SERIES E PREFERRED SHARES shall mean shares of Series E Preferred Stock
issued or issuable pursuant to the Series E Stock Purchase Agreement.

     SERIES E PREFERRED STOCK shall mean Series E Convertible Preferred Stock,
par value $.01 per share, of the Corporation.

     SERIES E STOCK PURCHASE AGREEMENT shall mean the Series E Convertible
Preferred Stock Purchase Agreement, dated May 22, 2001, as it may be amended
from time to time, among the Corporation and the Series E Investors listed on
Schedule 1 thereto.

     SERIES PREFERRED SHARES shall mean collectively the Series A Preferred
Shares, Series B Preferred Shares, Series C Preferred Shares, Series D Preferred
Shares and Series E Preferred Shares.

     STOCKHOLDERS shall mean all holders of capital stock of the Corporation.

     TARGET MONTH shall have the meaning set forth in Section 2.7(a) hereof.

     30-DAY PERIOD shall have the meaning set forth in Section 2.3(b) hereof.

     TRANSFER shall include any disposition of any Restricted Securities or of
any interest therein which would constitute a sale thereof within the meaning of
the Securities Act.

     1994 BRIDGE WARRANTS shall mean (i) the Common Stock Purchase Warrants
issued on or after July 27, 1994, to the persons or entities listed on the
signature page to the Credit Agreement (the "July Lenders"), in connection with
the execution and delivery of the Credit Agreement, dated July 27, 1994, among
the Corporation and the July Lenders and (ii) the Common Stock Purchase Warrants
issued on or after December 20, 1994, to the persons or entities listed on the
signature page to the Credit Agreement (the "December Lenders"), in connection
with the execution and delivery of the Credit Agreement dated December 20, 1994,
among the Corporation and the December Lenders.

     1995 BRIDGE WARRANTS shall mean the Common Stock Purchase Warrants to be
issued on or after June 20, 1995, to the persons or entities listed on the
signature page to the Credit Agreement (the "June 1995 Lenders"), in connection
with the execution and delivery of the Credit Agreement, dated June 20, 1995,
among the Corporation and the June 1995 Lenders.

     1996 BRIDGE WARRANTS shall mean (i) the Common Stock Purchase Warrants to
be issued on or after January 10, 1996, and on or before June 30, 1996, in
connection with the execution and delivery of one or more Credit Agreements,
dated on or after January 10, 1996, but on or before June 30, 1996, among the
Corporation and the parties signatory thereto and (ii) the Common Stock Purchase
Warrants to be issued on or after September 30, 1996, and on or before February
28, 1997, in connection with the execution and delivery of one or more Credit

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Agreements, dated on or after September 30, 1996, but on or before February 28,
1997, among the Corporation and the parties signatory thereto.

     1994 CAPITAL SUPPORT WARRANTS shall mean the Common Stock Purchase Warrants
issued to certain Investors in connection with the provision of a letter by each
such Investor to the Company's independent accountants committing to fund the
Company's cash flow requirements (up to a fixed amount) for the period ending
December 31, 1994.

     SECTION 2. CERTAIN COVENANTS OF THE CORPORATION.

          2.1   MEETINGS OF THE BOARD OF DIRECTORS. The Corporation shall call,
and use its best efforts to have, regular meetings of the Board not less often
than quarterly. The Corporation shall pay all reasonable and appropriately
documented travel expenses and other out-of-pocket expenses incurred by
directors who are not employed by the Corporation in connection with attendance
at meetings to transact the business of the Corporation or attendance at
meetings of the Board or any committee thereof.

          2.2   RESERVATION OF SHARES OF COMMON STOCK AND PREFERRED STOCK. The
Corporation shall at all times have authorized and reserved out of its
authorized but unissued shares of Common Stock, a sufficient number of shares of
Common Stock to provide for the conversion of the Series Preferred Shares.
Neither the issuance of the Series Preferred Shares nor the shares of Common
Stock issuable upon the conversion of the Series Preferred Shares shall be
subject to a preemptive right of any other Stockholder.

          2.3   RIGHT OF FIRST REFUSAL.

                (a)  The Corporation shall not issue, sell or exchange, agree to
issue, sell or exchange, or reserve or set aside for issuance, sale or exchange,
any Offered Securities unless in each case the Corporation shall have first
offered to sell to the Investors all of such Offered Securities, less only such
number of shares, in any venture capital round of financing, that shall be
offered to BWH (on the same terms, including but not limited to the price per
share, that such Offered Securities are offered to all other Investors) in order
to enable BWH to maintain its percentage ownership in the Corporation that
exists immediately prior to such venture capital round of financing (the "BWH
Securities"), on the terms set forth herein (as to all Investors, collectively,
and in the aggregate, the "Equity Percentage Securities"). Each Investor shall
be entitled to purchase up to its Equity Percentage of the Equity Percentage
Securities. Each Investor may delegate its rights and obligations with respect
to such Offer to one or more members of its Group, which members shall
thereafter be deemed to be "Investors" for the purpose of applying this Section
2.3 to such Offer.

                (b)  The Corporation shall deliver to each Investor written
notice of the offer to sell to such Investor its Equity Percentage of the Equity
Percentage Securities, and to BWH written notice of the offer to sell to BWH the
BWH Securities, specifying the price and terms and conditions of the offer
(each, an "Offer"). The Offer by its terms shall remain open and irrevocable for
a period of 30 days from the date of its delivery to such Investor or BWH, as

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the case may be (the "30-Day Period"), subject to extension solely with respect
to the Investors to include the Excess Securities Period (as such term is
hereinafter defined).

                (c)  Each Investor and BWH shall evidence its intention to
accept its Offer by delivering a written notice signed by the Investor or BWH,
as the case may be, setting forth the number of shares of the Equity Percentage
Securities or the BWH Securities that the Investor or BWH, respectively, elects
to purchase (the "Notice of Acceptance"). The Notice of Acceptance must be
delivered to the Corporation prior to the end of the 30-Day Period.

                (d)  If any Investor fails to exercise its right hereunder to
purchase all of its Equity Percentage of the Equity Percentage Securities, or if
BWH fails to exercise its right to purchase all of the BWH Securities, the
Corporation shall so notify the other Investors in a written notice (the "Excess
Securities Notice") . The Excess Securities Notice shall be given by the
Corporation promptly after it learns of the intentions of (i) all Investors with
respect to the purchase by each such Investor of less than all of its Equity
Percentage of the Equity Percentage Securities, or (ii) of BWH to purchase less
than all of the BWH Securities, but in no event later than ten (10) days after
the expiration of the 30-Day Period. The Investors who or which have agreed to
purchase their Equity Percentage of the Equity Percentage Securities shall have
the right to purchase the portion of the Equity Percentage Securities not
purchased by such Investor and the portion of the BWH Securities not purchased
by BWH (the "Excess Securities"), on a PRO RATA basis (as to each Investor,
calculated with respect to a percentage figure which expresses the ratio that
the number of shares of issued and outstanding Common Stock, on a fully diluted
basis, then owned by such Investor who or which has agreed to purchase its
Equity Percentage of the Offered Securities bears to the aggregate number of
shares of issued and outstanding Common Stock then owned by all Investors, on a
fully diluted basis, who or which have agreed to purchase their Equity
Percentage of the Offered Securities), by giving notice within ten (10) days
after receipt of the Excess Securities Notice from the Corporation. The twenty
(20) day period during which (i) the Corporation must give the Excess Securities
Notice to the other Investors, and (ii) each of the other Investors must give
the Corporation notice of its intention to purchase all or any portion of its
PRO RATA share of the its Excess Securities, is hereinafter referred to as the
"Excess Securities Period."

                (e)  If the Investors and BWH tender their Notices of Acceptance
prior to the end of the 30-Day Period indicating their intention to purchase all
of the Offered Securities or, if prior to the termination of the Excess
Securities Period, the Investors tender Excess Securities Notices to purchase
all of the Excess Securities, the Corporation shall schedule a closing of the
sale of all such Offered Securities. Upon the closing of the sale of the Offered
Securities to be purchased by the Investors, and subject to the closing of the
BWH Securities to be purchased by BWH, each Investor shall (i) purchase from the
Corporation that portion of the Equity Percentage Securities and the Excess
Securities for which it tendered a Notice of Acceptance and an Excess Securities
Notice, if applicable, upon the terms Specified in the Offer, and (ii) execute
and deliver an agreement further restricting transfer of such Equity Percentage
Securities substantially as set forth in Section 3.1, 3.2 and 3.3 of this
Agreement. In addition, with respect to the Offered Securities being purchased
by the Investors, the Corporation shall provide each such Investor with the
rights and benefits set forth in this Agreement. Upon the closing of the sale of
the BWH Securities to be purchased by BWH, BWH shall (i) purchase

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from the Corporation that portion of the BWH Securities for which it tendered a
Notice of Acceptance upon the terms specified in the Offer, and (ii) execute and
deliver an agreement further restricting transfer of such BWH Securities
substantially as set forth in Section 6 of the Stock Restriction Agreement dated
as of the date hereof between the Corporation and BWH. The obligation of the
Investors and BWH to purchase such Offered Securities is further conditioned
upon the preparation of a purchase agreement embodying the terms of the Offer,
which shall be reasonably satisfactory in form and substance to such Investors,
BWH and counsel for each of the Investors and BWH.

                (f)  If the Investors and BWH do not tender their Notices of
Acceptance prior to the end of the 30-Day Period, or if prior to the termination
of the Excess Securities Period, the Investors tender Excess Securities Notices
to purchase less than all of the Excess Securities, the Corporation shall have
ninety (90) days from the expiration of the 30-Day Period, or the Excess
Securities Period, if applicable, to sell the Offered Securities (including the
Excess Securities) refused by the Investors (the "Refused Securities") to any
other person or persons, but only upon terms and conditions which are in all
material respects (including, without limitation, price and interest rate) no
more favorable to such other person or persons, and no less favorable to the
Corporation, than those set forth in the Offer. Upon and subject to the closing
of the sale of all of the Refused Securities (which shall include full payment
to the Corporation), each Investor and BWH, as the case may be, shall (i)
purchase from the Corporation those Offered Securities (including, with respect
to the Investors, the Excess Securities) for which it tendered a Notice of
Acceptance and an Excess Securities Notice, if applicable, upon the terms
specified in the Offer, and (ii) execute and deliver an agreement restricting
transfer of such Offered Securities (including the Excess Securities)
substantially as set forth in Sections 3.1, 3.2 and 3.3 of this Agreement. In
addition, with respect to the Offered Securities being purchased by the
Investors, the Corporation shall provide each such Investor with the rights and
benefits set forth in this Agreement. The Corporation agrees, as a condition
precedent to accepting payment for and making delivery of any Refused Securities
to any executive officer, employee, consultant or independent contractor of or
to the Corporation, or to any other person, to have each and every such person
execute and deliver a Stock Restriction Agreement substantially in the form
attached hereto as EXHIBIT A, or as may be modified or amended from time to time
with the prior approval of the holders of a majority of the combined voting
power of the Series Preferred Shares then outstanding, calculated in accordance
with Section A.6 of Article III of the Certificate (including in such
calculation, any outstanding Restricted Shares held by such holders), to the
extent such purchaser has not already executed such Agreement. The obligation of
the Investors and BWH, as the case may be, to purchase such Offered Securities
(including, with respect to the Investors, the Excess Securities) is further
conditioned upon the preparation of a purchase agreement embodying the terms of
the Offer, which shall be reasonably satisfactory in form and substance to such
Investors, BWH and counsel for each of the Investors and BWH. Notwithstanding
the foregoing, it shall not be a condition to the acquisition of shares of
Preferred Stock pursuant to this Section 2.3 by such directors, officers,
employees, consultants or independent contractors of the Corporation that such
shares of Preferred Stock be subject to the restrictions imposed by a Stock
Restriction Agreement (other than the restrictions imposed by or arising out of
federal and state securities laws).

                                     - 12 -
<Page>

                (g)  In each case, any Offered Securities not purchased either
by the Investors, BWH or by any other person in accordance with this Section 2.3
may not be sold or otherwise disposed of until they are again offered to the
Investors under the procedures specified in Paragraphs (a), (b), (c), (d), (e)
and (f) hereof.

                (h)  Each Investor and BWH may, by prior written consent, waive
its rights under this Section 2.3. Such a waiver shall be deemed a limited
waiver and shall only apply to the extent specifically set forth in the written
consent of such Investor or BWH.

          2.4   NEGATIVE COVENANTS.

                (a)  SUPERMAJORITY APPROVALS. The Corporation shall not,
directly or indirectly, take any of the actions specified in Article III,
Section A.6(c) of the Certificate without the prior written consent or vote of
the Investors holding at least sixty five percent (65%) of the then outstanding
Series Preferred Shares held by Investors, determined in accordance with Section
A.6(a) of the Certificate.

                (b)  STOCK AND OPTION AGREEMENTS. Without the prior written
consent or vote of the Investors holding a majority of the then outstanding
Series Preferred Shares held by Investors, determined in accordance with Section
A.6(a) of Article III of the Certificate (including, in such calculation, any
outstanding Restricted Shares held by such Investors), the Corporation shall not
(i) issue any shares of Common Stock or options, warrants or other rights to
acquire Common Stock or other securities of the Corporation to any employee,
officer, director, consultant, independent contractor or other person or entity
except for Excluded Securities, (ii) grant any stock options with a per share
exercise price that is less than the fair market value of such shares of stock,
or (iii) make any restricted stock awards at a per share purchase price that is
less than the fair market value of the restricted stock, such fair market value
in the foregoing Subsection (ii) and in this subsection (iii) to be determined
by the Board of Directors.

                (c)  REGISTRATION RIGHTS. The Corporation shall not hereafter
grant to any persons any rights to register or qualify stock of the Corporation
under federal or state securities laws, unless it shall have first obtained the
written consent of Investors holding a majority of the then outstanding Series
Preferred Shares held by Investors, determined in accordance with Section A.6(a)
of Article III of the Certificate (including, in such calculation, any
outstanding Restricted Shares held by such holders).

          2.5   FILING OF REPORTS UNDER THE EXCHANGE ACT.

                (a)  The Corporation shall give prompt notice to the holders of
Series Preferred Shares of (i) the filing of any registration statement (an
"Exchange Act Registration Statement") pursuant to the Exchange Act, relating to
any class of equity securities of the Corporation, (ii) the effectiveness of
such Exchange Act Registration Statement, and (iii) the number of shares of such
class of equity Securities outstanding, as reported in such Exchange Act
Registration Statement, in order to enable the holders of Series Preferred
Shares to comply with any reporting requirements under the Exchange Act or the
Securities Act. Upon the written

                                     - 13 -
<Page>

request of a majority in interest of the holders of Series Preferred Shares, the
Corporation shall, at any time after the Corporation has registered any shares
of Common Stock under the Securities Act, file an Exchange Act Registration
Statement relating to any class of equity securities of the Corporation then
held by the holders of Series Preferred Shares or issuable upon conversion or
exercise of any class of debt or equity securities or warrants or options of the
Corporation then held by the Investors, whether or not the class of equity
securities with respect to which such request is made shall be held by the
number of persons which would require the filing of a registration statement
under Section 12(g)(1) of the Exchange Act.

                (b)  If the Corporation shall have filed an Exchange Act
Registration Statement or a registration statement (including an offering
circular under Regulation A promulgated under the Securities Act) pursuant to
the requirements of the Securities Act, which shall have become effective (and
in any event, at all times following the initial public offering of any of the
securities of the Corporation), then the Corporation shall comply with all of
the reporting requirements of the Exchange Act (whether or not it shall be
required to do so) and shall comply with all other public information reporting
requirements of the Commission as a condition to the availability of an
exemption from the Securities Act for the sale of any of the Restricted
Securities by any holder of Restricted Securities (including any such exemption
pursuant to Rule 144 or Rule 144A thereof, as amended from time to time, or any
Successor rule thereto or otherwise). The Corporation shall cooperate with each
holder of Restricted Securities in supplying such information as may be
necessary for such holder of Restricted Securities to complete and file any
information reporting forms presently or hereafter required by the Commission as
a condition to the availability of an exemption from the Securities Act (under
Rule 144 or Rule 144A thereunder or otherwise) for the sale of any of the
Restricted Securities by any holder of Restricted Securities.

          2.6   ACCESS TO RECORDS. Until such time that the Corporation has a
class of its equity securities registered under the Exchange Act and is required
to file reports thereunder pursuant to Sections 13 or 15(d) of the Exchange Act,
the Corporation shall afford to each Major Investor and such Major Investor's
employees, counsel and other authorized representatives, free and full access,
at all reasonable times and for reasonable periods of time, to all of the books,
records and properties of the Corporation and to all officers and employees of
the Corporation.

          2.7   FINANCIAL REPORTS. Until such time that the Corporation has a
class of its equity securities registered under the Exchange Act and is required
to file reports thereunder pursuant to Sections 13 or 15(d) of the Exchange Act,
except with respect to the obligation set forth in Section 2.7(e)(i) hereunder
which shall survive such time, the Corporation shall furnish each Major Investor
with the financial information described below:

                (a)  Within 20 days after the last day of each month (the
"Target Month") (or such other calendar period as is approved by the Board),
financial statements, including a balance sheet as of the last day of such
Target Month, a statement of income (or monthly operating expenses) for such
month, together with a cumulative statement of income from the first day of the
current year to the last day of such Target Month, which statements shall be
prepared from the books and records of the Corporation, a cash flow analysis,
together with cumulative cash flow analyses from the first day of the current
year to the last day of such

                                     - 14 -
<Page>

month, and a comparison between the actual monthly operating expenses and the
projected figures for such month and the comparable figures for the prior year,
subject to the provisions of Section 2.9 hereof.

                (b)  Upon receipt of a request from any of the Major Investors
prior to the end of a quarterly accounting period, the Corporation shall deliver
to each of the Major Investors, within 45 days after the end of such quarterly
accounting period, unaudited financial statements for such quarterly accounting
period, certified by the Chief Financial Officer or the Treasurer of the
Corporation, as presenting fairly the financial condition and results of
operations of the Corporation and as having been prepared on a basis consistent
with the accounting Principles reflected in the Corporation's annual audited
financial statements, accompanied by a report, Signed by the Chief Financial
Officer or the Treasurer of the Corporation, summarizing the operating and
financial highlights of the Corporation for such quarterly accounting period,
which report shall include (i) a comparison between the actual quarterly
operating and financial results, the Budget (as defined in Section 2.8 hereof)
and the results of the similar quarterly accounting period for the prior fiscal
year of the Corporation, together with an explanation of material variances from
the Budget and such similar quarterly accounting period, as the case may be, and
(ii) a narrative analysis of operations and trends in the business of the
Corporation during such quarterly accounting period.

                (c)  Within 90 days after the end of each fiscal year of the
Corporation, audited financial statements of the Corporation, which shall
include an income statement and a statement of cash flow for such fiscal year
and a balance sheet as of the last day thereof, each prepared in accordance with
generally accepted accounting principles consistently applied, and accompanied
by the report of such independent certified public accountants as shall have
been approved by the Board.

                (d)  If for any period the Corporation shall have any subsidiary
or subsidiaries whose accounts are consolidated with those of the Corporation,
then the financial statements delivered for such period pursuant to paragraphs
(a), (b) and (c) of this Section 2.7 shall be the consolidated and consolidating
financial statements of the Corporation for all such consolidated subsidiaries.

                (e)  Promptly upon becoming available:

                     (i)   copies of all financial statements, reports, press
releases, notices, proxy statements and other documents sent by the Corporation
to its Stockholders or released to the public and copies of all regular and
periodic reports, if any, filed by the Corporation with the Commission or any
securities exchange or self-regulatory organization; and

                     (ii)  any other financial or other information available to
management of the Corporation that any of the Major Investors shall have
reasonably requested on a timely basis.

          2.8   BUDGET AND OPERATING FORECAST. Until such time that the
Corporation has a class of its equity securities registered under the Exchange
Act and is required to file reports

                                     - 15 -
<Page>

thereunder pursuant to Sections 13 or 15(d) of the Exchange Act, the Corporation
shall prepare and submit to the Board and each of the Major Investors an
operating plan with monthly and quarterly breakdowns (the "Budget") for each
fiscal year at least 45 days prior to the beginning of each fiscal year of the
Corporation. The Budget shall be deemed accepted as the Budget for such fiscal
year only when it has been approved by the Board. The Budget shall be reviewed
by the Corporation periodically and all changes therein, and all material
deviations therefrom, shall be reviewed by the Board on at least a quarterly
basis.

          2.9   SYSTEM OF ACCOUNTING. The Corporation shall maintain, and cause
each of its subsidiaries, when and if any shall exist, to maintain, its books of
accounts, related records and system of accounting in accordance with good
business practices and generally accepted accounting principles, and shall cause
the matters contained therein to be appropriately and accurately reflected in
the financial reports (which shall be prepared in accordance with generally
accepted accounting principles) furnished pursuant to this Agreement.

          2.10  RESTRICTION ON TRANSFER RIGHTS. The rights granted to each Major
Investor pursuant to Sections 2.6 through 2.8 hereof shall not be transferred or
assigned by any Investor to, and shall not inure to the benefit of, any
successor, transferee or assignee of any Investor, which is engaged in any line
of business directly competitive with the Corporation.

          2.11  CONFIDENTIALITY AND NON-COMPETITION AGREEMENTS FOR KEY
EMPLOYEES. The Corporation shall cause each person who is presently an employee
of or a consultant or independent contractor to the Corporation or who becomes
an employee of or a consultant to the Corporation subsequent to the date hereof
and who shall have or be proposed to have access to confidential or proprietary
information of the Corporation to execute a confidentiality and non-competition
agreement in form and substance attached hereto or otherwise approved by the
Board prior to the commencement of such person's employment by the Corporation
in such capacity.

          2.12  STOCK RESTRICTION AGREEMENT FOR DIRECTORS, OFFICERS EMPLOYEES
AND CONSULTANTS WHO ARE OR BECOME STOCKHOLDERS. The Corporation shall cause each
of its directors, officers, employees, consultants or independent contractors
who own any shares of capital stock of the Corporation, or exercises any
options, warrants or other rights to purchase any shares of such capital stock,
or who may own in the future any such shares, or options, warrants or other
rights to purchase such shares, to execute a Stock Restriction Agreement
substantially in the form attached hereto as EXHIBIT A, and as may be modified
and amended from time to time with the approval of the holders of a majority of
the combined voting power of the Series Preferred Shares then outstanding,
determined in accordance with Section A.6(a) of Article III of the Certificate
(including, in such calculation, any outstanding Restricted Shares held by such
holders), prior and as a condition to the acquisition of such shares, or
options, warrants or rights, by such person. Notwithstanding the foregoing, it
shall not be a condition to the acquisition of shares of Preferred Stock
pursuant to Section 2.3 hereof by such directors, officers, employees,
consultants or independent contractors of the Corporation that such shares of
Preferred Stock be subject to the restrictions imposed by a Stock Restriction
Agreement (other than the restrictions imposed by or arising out of federal and
state securities laws)

                                     - 16 -
<Page>

          2.13  MARKETING AND PROMOTIONAL MATERIAL. Each of the Investors will
have the right to review and approve, in advance of publication, distribution or
dissemination, any reference to such Investor or any entity affiliated with such
Investor (other than the Corporation), contained in any document, instrument,
report or filing or in any advertising, marketing, promotional and similar
materials.

          2.14  ENVIRONMENTAL MATTERS. The Corporation shall promptly advise the
Investors in writing of any pending or threatened claim, demand or action by any
governmental authority or third party relating to any Hazardous Materials
affecting the Property or of any failure to materially comply with the
Environmental Laws, in each case of which it has knowledge. The Corporation
shall not discharge, place, release, spill or dispose of any Hazardous Materials
or any other pollutants or effluents upon the Property or elsewhere (including,
but not limited to, underground injection of such substances), and the
Corporation shall not discharge into the air any emission which would require a
permit under the Clean Air Act or its state counterparts or any other
Environmental Laws, except in compliance with the Environmental Laws. The
Stockholders of the Corporation shall have no control over, or authority with
respect to, the waste disposal operations of the Corporation. The Corporation
hereby indemnifies, defends and holds harmless the Investors from and against
any and all manner of actions, causes of action, suits, debts, accounts,
controversies, judgments, claims, demands, losses or liabilities of any nature
(including reasonable attorneys' fees) directly or indirectly arising out of or
attributable to (a) any misrepresentation or breach of the representations and
covenants set forth in Section 5.17 of the Series E Stock Purchase Agreement, or
(b) the use, generation, storage, release, threatened release, discharge,
disposal or presence of Hazardous Materials on, under or about the Property by
any person during the period that the Corporation was the legal or equitable
owner of the Property or which occurred prior to such time and was otherwise
actually known by, or should have been known by, the Corporation. The obligation
of the Corporation to indemnify the Investors shall specifically cover and
include, without limitation, all fines and penalties imposed by federal, state
or local authorities, costs of removing or neutralizing the Hazardous Materials,
injury to the property adjoining the Property, injury to persons living or
working on or about the Property or adjoining or otherwise affecting property,
and all other indirect or consequential damages incurred by the Investors.

          2.15  TERMINATION OF COVENANTS. The covenants set forth in this
Section 2 (other than Sections 2.5, 2.11, 2.13 and the indemnities provided in
Section 2.14) shall terminate upon the closing of an Initial Public Offering.

     SECTION 3. TRANSFER OF SECURITIES; REGISTRATION RIGHTS.

          3.1   RESTRICTION ON TRANSFER. The Restricted Securities shall not be
transferable, except upon the conditions specified in this Section 3, which
conditions are intended solely to ensure compliance with the provisions of the
Securities Act in respect of the Transfer thereof.

          3.2   RESTRICTIVE LEGEND. Each certificate evidencing any Restricted
Securities and each certificate evidencing any such securities issued to
subsequent transferees of any

                                     - 17 -
<Page>

Restricted Securities shall (unless otherwise permitted by the provisions of
Section 3.3 or 3.10 hereof) be stamped or otherwise imprinted with a legend in
substantially the following form:

          THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE BEEN
          ACQUIRED FOR INVESTMENT AND HAVE NOT BEEN REGISTERED UNDER
          THE SECURITIES ACT OF 1933, AS AMENDED, OR ANY STATE
          SECURITIES LAW. THE SECURITIES MAY NOT BE PLEDGED,
          HYPOTHECATED, SOLD OR TRANSFERRED IN THE ABSENCE OF AN
          EFFECTIVE REGISTRATION STATEMENT FOR THE SECURITIES UNDER
          THE SECURITIES ACT OF 1933 OR ANY APPLICABLE STATE
          SECURITIES LAW OR AN EXEMPTION THEREFROM UNDER SUCH ACT OR
          LAW. ADDITIONALLY, THE TRANSFER OF THESE SECURITIES IS
          SUBJECT TO THE CONDITIONS SPECIFIED IN A STOCKHOLDERS'
          AGREEMENT AMONG NITROMED, INC. AND CERTAIN OTHER SIGNATORIES
          THERETO, AND NO TRANSFER OF SUCH SECURITIES SHALL BE VALID
          OR EFFECTIVE UNTIL SUCH CONDITIONS HAVE BEEN FULFILLED.
          COPIES OF SUCH AGREEMENT MAY BE OBTAINED AT NO COST BY
          WRITTEN REQUEST MADE BY THE HOLDER OF RECORD OF THIS
          CERTIFICATE TO THE SECRETARY OF NITROMED, INC.

          3.3   NOTICE OF TRANSFER. By acceptance of any Restricted Securities,
the holder thereof agrees to give prior written notice to the Corporation of
such holder's intention to effect any Transfer and to comply in all other
respects with the provisions of this Section 3.3. Each such notice shall
describe the manner and circumstances of the proposed Transfer and shall be
accompanied by: (a) the written opinion of counsel for the holder of such
Restricted Securities, or, at such holder's option, a representation letter of
such holder, addressed to the Corporation (which opinion and counsel, or
representation letter, as the case may be, shall be reasonably acceptable to the
Corporation), as to whether, in the case of a written opinion, in the opinion of
such counsel, such proposed Transfer involves a transaction requiring
registration of such Restricted Securities under the Securities Act and
applicable state securities laws or an exemption thereunder is available, or, in
the case of a representation letter, such letter sets forth a factual basis for
concluding that such proposed transfer involves a transaction requiring
registration of such Restricted Securities under the Securities Act and
applicable State Securities laws or that an exemption thereunder is available,
or (b) if such registration is required and if the provisions of Section 3.4
hereof are applicable, a written request addressed to the Corporation by the
holder of such Restricted Securities, describing in detail the proposed method
of disposition and requesting the Corporation to effect the registration of such
Restricted Shares pursuant to the terms and provisions of Section 3.4 hereof;
PROVIDED, HOWEVER, that (y) in the case of a transfer by a holder to a member of
such holder's Group, no such opinion of counsel or representation letter of the
holder shall be necessary, provided that the transferee agrees in writing to be
subject to Sections 3.1, 3.2, 3.3 and 3.10 hereof to the same extent as if such
transferee were originally a

                                     - 18 -
<Page>

signatory to this Agreement, and (z) in the case of any holder of Restricted
Securities that is a partnership, no such opinion of counsel or representation
letters of the holder shall be necessary for a transfer by such holder to a
partner of such holder, or a retired partner of such holder who retires after
the date hereof, or the estate of any such partner or retired partner if, with
respect to such transfer by a partnership, (i) such transfer is made in
accordance with the partnership agreement of such partnership, and (ii) the
transferee agrees in writing to be subject to the terms of Sections 3.1, 3.2,
3.3 and 3.10 hereof to the same extent as if such transferee were originally a
signatory to this Agreement. If in such opinion of counsel or as reasonably
concluded from the facts set forth in the representation letter of the holder
(which opinion and counsel, or representation letter, as the case may be, shall
be reasonably acceptable to the Corporation), the proposed transfer may be
effected without registration under the Securities Act and any applicable state
securities laws or "blue sky" laws, then the holder of Restricted Securities
shall thereupon be entitled to effect such transfer in accordance with the terms
of the notice delivered by it to the Corporation. Each certificate or other
instrument evidencing the securities issued upon such Transfer (and each
certificate or other instrument evidencing any such securities not Transferred)
shall bear the legend set forth in Section 3.2 hereof unless: (a) in such
opinion of such counsel or as can be concluded from the representation letter of
such holder (which opinion and counsel or representation letter shall be
reasonably acceptable to the Corporation) the registration of future Transfers
is not required by the applicable provisions of the Securities Act and state
securities laws, or (b) the Corporation shall have waived the requirement of
such legend; PROVIDED, HOWEVER, that such legend shall not be required on any
certificate or other instrument evidencing the securities issued upon such
Transfer in the event such Transfer shall be made in compliance with the
requirements of Rule 144 (as amended from time to time or any similar or
successor rule) promulgated under the Securities Act. The holder of Restricted
Securities shall not effect any Transfer until such opinion of counsel or
representation letter of such holder has been given to and reasonably accepted
by the Corporation (unless waived by the Corporation) or until registration of
the Restricted Shares involved in the above- mentioned request has become
effective under the Securities Act. In the event that an opinion of counsel is
required by the registrar or transfer agent of the Corporation to effect a
transfer of Restricted Securities in the future, the Corporation shall seek and
obtain such opinion from its counsel, and the holder of such Restricted
Securities shall provide such reasonable assistance as is requested by the
Corporation (other than the furnishing of an opinion of counsel) to satisfy the
requirements of the registrar or transfer agent to effectuate such transfer.

          3.4   REQUIRED REGISTRATION. If, at any time following the earlier of
(a) December 31, 2003, or (b) the closing of an Initial Public Offering, the
Corporation shall be requested (i) by Investors holding at least 40% of the
aggregate outstanding Restricted Securities held by all Investors (based on the
underlying Common Stock for which the Restricted Securities are convertible or
exercisable) to effect the registration under the Securities Act of Restricted
Shares, or (ii) after the first registration pursuant to this Section 3.4, by
one or more of the Investors holding Restricted Securities to effect the
registration under the Securities Act of Restricted Shares having a proposed
aggregate offering price equal to or greater than $1,000,000, then the
Corporation shall promptly give written notice of such proposed registration to
all holders of Restricted Securities, and thereupon the Corporation shall
promptly use its best efforts to effect the registration under the Securities
Act of the Restricted Shares that the Corporation has been requested to register
for disposition as described in the request of such holders of

                                     - 19 -
<Page>

Restricted Securities and in any response received from any of the holders of
Restricted Securities within 30 days after the giving of the written notice by
the Corporation; PROVIDED, HOWEVER, that the Corporation shall not be obligated
to effect any registration under the Securities Act except in accordance with
the following provisions and Section 3.6:

                (a)  Subject to Section 3.6, the Corporation shall not be
obligated to file and cause to become effective more than two (2) registration
statements in which Restricted Shares are registered under the Securities Act
pursuant to this Section 3.4, if all of the Restricted Shares offered pursuant
to such registration statements are sold thereunder upon the price and terms
offered.

                (b)  Notwithstanding the foregoing, the Corporation may include
in each such registration requested pursuant to this Section 3.4 any authorized
but unissued shares of Common Stock (or authorized treasury shares) for sale by
the Corporation or any issued and outstanding shares of Common Stock for sale by
others; PROVIDED, HOWEVER, that, if the number of shares of Common Stock so
included pursuant to this clause (b) exceeds the number of Restricted Shares
requested by the holders of Restricted Shares requesting such registration, then
such registration shall be deemed to be a registration in accordance with and
pursuant to Section 3.5; and PROVIDED FURTHER, HOWEVER, that the inclusion of
such previously authorized but unissued shares by the Corporation or issued and
outstanding shares of Common Stock by others in such registration does not
adversely affect, in the sole opinion of the holders of Restricted Securities
requesting such registration, the ability of the holders of Restricted
Securities requesting such registration to market the entire number of
Restricted Shares requested by them.

          3.5   PIGGYBACK REGISTRATION.

                (a)  Each time that the Corporation proposes for any reason to
register any of its securities under the Securities Act, other than pursuant to
a registration statement on Form S-4 or Form S-8 or similar or successor forms
or pursuant to a transaction under Rule 145 of the Securities Act (collectively,
"Excluded Forms"), the Corporation shall promptly give written notice of such
proposed registration to all holders of Restricted Securities, which shall offer
such holders the right to request inclusion of any Restricted Shares in the
proposed registration.

                (b)  Each holder of Restricted Securities shall have 30 days
from the receipt of such notice to deliver to the Corporation a written request
specifying the number of Restricted Shares such holder intends to sell and the
holder's intended method of disposition.

                (c)  In the event that the proposed registration by the
Corporation is, in whole or in part, an underwritten public offering of
securities of the Corporation, any request under Section 3.5(b) may specify that
the Restricted Shares be included in the underwriting (i) on the same terms and
conditions as the shares of Common Stock, if any, otherwise being sold through
underwriters under such registration, or (ii) on terms and conditions comparable
to those normally applicable to offerings of common stock in reasonably similar
circumstances in the event that no shares of Common Stock other than Restricted
Shares are being sold through underwriters under such registration.

                                     - 20 -
<Page>

                (d)  Upon receipt of a written request pursuant to Section
3.5(b), the Corporation shall promptly use its best efforts to cause all such
Restricted Shares to be registered under the Securities Act, to the extent
required to permit sale or disposition as set forth in the written request.

                (e)  Notwithstanding the foregoing, if the managing underwriter
of any such proposed registration determines and advises in writing that the
inclusion of all Restricted Shares proposed to be included in the underwritten
public offering, together with any other issued and outstanding shares of Common
Stock proposed to be included therein by holders other than the holders of
Restricted Securities (such other shares hereinafter Collectively referred to as
the "Other Shares"), would interfere with the successful marketing of the
Corporation's securities, then the total number of such securities proposed to
be included in such underwritten public offering shall be reduced, (i) first by
the shares requested to be included in such registration by the holders of Other
Shares, and (ii) second, if necessary, (A) one-half (1/2) by the securities
proposed to be issued by the Corporation, and (B) one-half (1/2) by the
Restricted Shares proposed to be included in such registration by the holders
thereof, on a PRO RATA basis, based upon the number of Restricted Shares sought
to be registered by each such holder. The shares of Common Stock that are
excluded from the underwritten public offering pursuant to the preceding
sentence shall be withheld from the market by the holders thereof for a period,
not to exceed 180 days from the closing of such underwritten public offering,
that the managing underwriter reasonably determines as necessary in order to
effect such underwritten public offering.

          3.6   REGISTRATIONS ON FORM S-2 AND S-3. At such time as the
Corporation shall have qualified for the use of Form S-2 or Form S-3 (or any
successor form promulgated under the Securities Act), the holders of Restricted
Securities shall have the right to request in writing up to two (2)
registrations on Form S-2 or Form S-3 in any twelve-month period. Each such
request by a holder shall: (a) specify the number of Restricted Shares which the
holder intends to sell or dispose of, (b) state the intended method by which the
holder intends to sell or dispose of such Restricted Shares, and (c) request
registration of Restricted Shares having a proposed aggregate offering price of
at least $500,000. Upon receipt of a request pursuant to this Section 3.6, the
Corporation shall provide written notice to all other holders of Restricted
Securities of such request and the provisions of Section 3.5 shall govern the
inclusion of additional Restricted Securities in such registration. The
Corporation shall use its best efforts to effect such registration or
registrations on Form S-2 or Form S-3.

          3.7   PREPARATION AND FILING. If and whenever the Corporation is under
an obligation pursuant to the provision of this Section 3 to use its best
efforts to effect the registration of any Restricted Shares, the Corporation
shall, as expeditiously as practicable:

                (a)  prepare and file with the Commission a registration
statement with respect to such securities and use its best efforts to cause such
registration statement to become and remain effective in accordance with Section
3.7(b) hereof;

                (b)  prepare and file with the Commission such amendments and
supplements to such registration statement and the prospectus used in connection
therewith as

                                     - 21 -
<Page>

may be necessary to keep such registration statement effective until the earlier
of (i) the sale of all Restricted Shares covered thereby or (ii) nine months,
and to comply with the provisions of the Securities Act with respect to the sale
or other disposition of all Restricted Shares covered by such registration
statement;

                (c)  furnish to each holder whose Restricted Shares are being
registered pursuant to this Section 3 such number of copies of any summary
prospectus or other prospectus, including a Preliminary Prospectus, in
conformity with the requirements of the Securities Act, and such other documents
as such holder may reasonably request in order to facilitate the public sale or
other disposition of such Restricted Shares;

                (d)  use its best efforts to register or qualify the Restricted
Shares covered by such registration statement under the securities or blue sky
laws of such jurisdictions as each holder whose Restricted Shares are being
registered pursuant to this Section 3 shall reasonably request and do any and
all other acts or things which may be necessary or advisable to enable such
holder to consummate the public sale or other disposition in such jurisdictions
of such Restricted Shares; PROVIDED, HOWEVER, that the Corporation shall not be
required to consent to general service of process for all purposes in any
jurisdiction where it is not then subject to process, qualify to do business as
a foreign corporation where it would not be otherwise required to qualify or
submit to liability for state or local taxes where it is not otherwise liable
for such taxes;

                (e)  at any time when a prospectus covered by such registration
statement and relating thereto is required to be delivered under the Securities
Act within the appropriate period mentioned in Section 3.7(b) hereof, notify
each holder whose Restricted Shares are being registered pursuant to this
Section 3 of the happening of any event as a result of which the prospectus
included in such registration, 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, at the request of such holder, prepare,
file and furnish to such holder a reasonable number of copies of a supplement to
or an amendment of such prospectus as may be necessary so that, as thereafter
delivered to the purchasers of such shares, such prospectus shall not include an
untrue statement of a material fact or omit 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;

                (f)  if the Corporation has delivered preliminary or final
prospectuses to the holders of Restricted Shares that are being registered
pursuant to this Section 3 and after having done so the prospectus is amended to
comply with the requirements of the Securities Act, the Corporation shall
promptly notify such holders and, if requested, such holders shall immediately
cease making offers of Restricted Shares and return all prospectuses to the
Corporation. The Corporation shall promptly provide such holders with revised
prospectuses and, following receipt of the revised prospectuses, such holders
shall be free to resume making offers of the Restricted Shares; and

                (g)  furnish, at the request of any holder whose Restricted
Shares are being registered pursuant to this Section 3, on the date that such
Restricted Shares are delivered

                                     - 22 -
<Page>

to the underwriters for sale in connection with a registration pursuant to this
Section 3, if such securities are being sold through underwriters, or, on the
date that the registration statement with respect to such securities becomes
effective, if such securities are not being sold through underwriters, (i) an
opinion, dated such date, of the counsel representing the Corporation for the
purposes of such registration, in form and substance as is customarily given to
underwriters in an underwritten public offering, addressed to the underwriters,
if any, and to the holder or holders making such request, and (ii) a letter
dated such date, from the independent certified public accountants of the
Corporation, in form and substance as is customarily given by independent
certified public accountants to underwriters in an underwritten public offering,
addressed to the underwriters, if any, and to the holder or holders making such
request.

          3.8   EXPENSES. The Corporation shall pay all expenses incurred by the
Corporation in complying with this Section 3, including, without limitation, all
registration and filing fees (including all expenses incident to filing with the
National Association of Securities Dealers, Inc.), fees and expenses of
complying with the securities and blue sky laws of all such jurisdictions in
which the Restricted Shares are proposed to be offered and sold, printing
expenses and fees and disbursements of counsel (including with respect to each
registration effected pursuant to Sections 3.4, 3.5 and 3.6, the reasonable fees
and disbursements of counsel for the Investors, as selling Stockholder(s)
thereunder that are being registered pursuant to this Section 3); PROVIDED,
HOWEVER, that all underwriting discounts and selling commissions applicable to
the Restricted Shares covered by registrations effected pursuant to Section 3.4,
3.5 or 3.6 hereof shall be borne by the seller or sellers thereof, in proportion
to the number of Restricted Shares sold by each such seller or sellers.

          3.9   INDEMNIFICATION.

                (a)  In the event of any registration of any Restricted Shares
under the Securities Act pursuant to this Section 3 or registration or
qualification of any Restricted Shares pursuant to Section 3.7(d) hereof, the
Corporation shall indemnify and hold harmless the seller of such shares, each
underwriter of such shares, if any, each broker or any other person acting on
behalf of such seller and each other person, if any, who controls any of the
foregoing persons, within the meaning of the Securities Act or the Exchange Act,
against any losses, claims, damages or liabilities, joint or several, to which
any of the foregoing persons may become subject under the Securities Act or the
Exchange Act or otherwise, insofar as such losses, claims, damages or
liabilities (or actions in respect thereof) arise out of or are based upon an
untrue statement or alleged untrue statement of a material fact contained in any
registration statement under which such Restricted Shares were registered under
the Securities Act, any preliminary prospectus or final prospectus contained
therein, or any amendment or supplement thereto, or any document incident to
registration or qualification of any Restricted Shares pursuant to Section
3.7(d) hereof, or arise out of or are based upon the 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, with respect to any
prospectus, necessary to make the statements therein, in light of the
circumstances under which they were made, not misleading, or any violation by
the Corporation of the Securities Act or the Exchange Act or any state
securities or blue sky laws applicable to the Corporation and relating to action
or inaction required of the Corporation in connection with such registration or
qualification under the Securities Act or the Exchange Act

                                     - 23 -
<Page>

or such state securities or blue sky laws. The Corporation shall reimburse on
demand such seller, underwriter, broker or other person acting on behalf of such
seller and each such controlling person for any legal or any other expenses
reasonably incurred by any of them in connection with investigating or defending
any such loss, claim, damage, liability or action; PROVIDED, HOWEVER, that the
Corporation shall not be liable in any such case to the extent that any such
loss, claim, damage or liability arises out of or is based upon an untrue
statement or alleged untrue statement or omission or alleged omission made in
said registration statement, preliminary or final prospectus or amendment or
supplement thereto or any document incident to registration or qualification of
any Restricted Shares pursuant to Section 3.7(d) hereof, in reliance upon and in
conformity with written information furnished to the Corporation by such seller,
underwriter, broker, other person or controlling person specifically for use in
the preparation thereof.

                (b)  Before Restricted Shares held by any prospective seller
shall be included in any registration pursuant to this Section 3, such
prospective seller shall have agreed to indemnify and hold harmless (in the same
manner and to the same extent as set forth in paragraph (a)) the Corporation,
each director of the Corporation, each officer of the Corporation who signs such
registration statement and any person who controls the Corporation within the
meaning of the Securities Act or the Exchange Act, with respect to any untrue
statement or omission from such registration statement, any preliminary
prospectus or final prospectus contained therein, or any amendment or supplement
thereto, if such untrue statement or omission was made in reliance upon and in
conformity with written information furnished to the Corporation through an
instrument duly executed by such seller specifically for use in the preparation
of such registration statement, preliminary prospectus, final prospectus or
amendment or supplement; PROVIDED, HOWEVER, that the maximum amount of liability
in respect of such indemnification shall be limited, in the case of each
prospective seller, to an amount equal to the net proceeds actually received by
such prospective seller from the sale of Restricted Shares effected pursuant to
such registration and PROVIDED FURTHER, that no prospective seller shall be
required to make any representations or warranties to the Corporation or the
underwriters (other than representations and warranties regarding such
prospective seller, its title to the Restricted Shares to be sold and its
intended method of distribution thereof), or to undertake any indemnification
obligations to the Corporation or to the underwriters with respect thereto,
except as otherwise provided by this Section 3(b).

                (c)  Promptly after receipt by an indemnified party of notice of
the commencement of any action involving a claim referred to in Section 3.9(a)
or (b) hereof, such indemnified party will, if a claim in respect thereof is to
be made against the indemnifying party under this Section 3.9, give written
notice to the latter of the commencement of such action. In case any such action
is brought against an indemnified party, the indemnifying party will be entitled
to participate in and to assume the defense thereof, jointly with any other
indemnifying party similarly notified to the extent that it may wish, with
counsel reasonably satisfactory to such indemnified party, and, after notice to
such indemnified party from the indemnifying party of its election to assume the
defense thereof, the indemnifying party shall be responsible for any legal or
other expenses subsequently incurred by it in connection with the defense
thereof; PROVIDED, HOWEVER, that, if any indemnified party shall have reasonably
concluded that there may be one or more legal defenses available to such
indemnified party which are different from or additional to those available to
the indemnifying party, or that such claim or litigation involves or

                                     - 24 -
<Page>

could have an effect upon matters beyond the scope of the indemnity agreement
provided in this Section 3.9, the indemnifying party shall not have the right to
assume the defense of such action on behalf of such indemnified party, and such
indemnifying party shall reimburse such indemnified party and any person
controlling such indemnified party for the fees and expenses of counsel retained
by the indemnified party which are reasonably related to the matters covered by
the indemnity agreement provided in this Section 3.9. The indemnifying party
shall not make any settlement of any claims indemnified against hereunder
without the written consent of the indemnified party or parties, which consent
shall not be unreasonably withheld.

                (d)  In order to provide for just and equitable contribution to
joint liability under the Securities Act or the Exchange Act in any case in
which either (i) any holder of Restricted Shares exercising rights under this
Agreement, or any controlling person of any such holder, makes a claim for
indemnification pursuant to this Section 3.9, but it is judicially determined
(by the entry of a final judgment or decree by a court of competent jurisdiction
and the expiration of time to appeal or the denial of the last right of appeal)
that such indemnification may not be enforced in such case notwithstanding the
fact that this Section 3.9 provides for indemnification in such case, or (ii)
contribution under the Securities Act may be required on the part of any such
holder or any such controlling person in circumstances for which indemnification
is provided under this Section 3.9; then, in each such case, the Corporation and
such holder will contribute to the aggregate losses, claims, damages or
liabilities to which they may be subject as is appropriate to reflect the
relative fault of the Corporation and such holder in connection with the
statements or omissions which resulted in such losses, claims, damages or
liabilities, it being understood that the parties acknowledge that the
overriding equitable consideration to be given effect in connection with this
provision is the ability of one party or the other to correct the statement or
omission which resulted in such losses, claims, damages or liabilities, and that
it would not be just and equitable if contribution pursuant hereto were to be
determined by PRO RATA allocation or by any other method of allocation which
does not take into consideration the foregoing equitable considerations.
Notwithstanding the foregoing, (i) no such holder will be required to contribute
any amount in excess of the proceeds to it of all Restricted Shares sold by it
pursuant to such registration statement, and (ii) no person or entity guilty of
fraudulent misrepresentation, within the meaning of Section 11(f) of the
Securities Act, shall be entitled to contribution from any person or entity who
is not guilty of such fraudulent misrepresentation.

                (e)  The Corporation shall use its best efforts to ensure that
indemnification provisions adopted in any underwriting agreement are no more
restrictive than as set forth herein. Notwithstanding any of the foregoing, if,
in connection with an underwritten public offering of any Restricted Shares, the
Corporation, the holders of such Restricted Shares and the underwriters enter
into an underwriting or purchase agreement relating to such offering which
contains provisions covering indemnification among the parties, then the
indemnification provision of this Section 3.9 shall be deemed inoperative for
purposes of such offering.

          3.10  REMOVAL OF LEGENDS, ETC. Notwithstanding the foregoing
provisions of this Section 3, the restrictions imposed by this Section 3 upon
the transferability of any Restricted Securities shall cease and terminate when
(a) any such Restricted Securities are sold or otherwise disposed of in
accordance with the intended method of disposition by the seller or

                                     - 25 -
<Page>

sellers thereof set forth in a registration statement or such other method
contemplated by Section 3.3 hereof that does not require that the securities
transferred bear the legend set forth in Section 3.2 hereof, including a
Transfer pursuant to Rule 144 or a successor rule thereof (as amended from time
to time), or (b) the holder of Restricted Securities has met the requirements
for transfer of such Restricted Securities pursuant to Subparagraph (k) of Rule
144 or a successor rule thereof (as amended from time to time) promulgated by
the Commission under the Securities Act. Whenever the restrictions imposed by
this Section 3 have terminated, a holder of a certificate for Restricted
Securities as to which such restrictions have terminated shall be entitled to
receive from the Corporation, without expense, a new certificate not bearing the
restrictive legend set forth in Section 3.2 hereof and not containing any other
reference to the restrictions imposed by this Section 3.

          3.11  GRANTS OF REGISTRATION RIGHTS. The Corporation shall not grant
registration rights to any holder of securities of the Corporation (other than
the rights granted pursuant to this Agreement) without the prior written consent
of the holders of a majority in voting power of the Series Preferred Shares and
the Common Stock issued upon the conversion thereof. Any registration rights so
granted shall in any case be no more favorable than those granted hereby.

     SECTION 4. SECURITIES ACT REGISTRATION STATEMENTS. Except for securities of
the Corporation registered on Excluded Forms, the Corporation shall not file any
registration statement under the Securities Act covering any securities unless
it shall first have given each holder of Restricted Securities written notice
thereof. The Corporation further covenants that each holder of Restricted
Securities shall have the right, at any time when it may be deemed to be a
controlling person of the Corporation, within the meaning of the Securities Act,
to participate in the preparation of such registration statement and to request
the insertion therein of material furnished to the Corporation in writing which
in such holder's judgment should be included. In connection with any
registration statement referred to in this Section 4, the Corporation shall
indemnify, to the extent permitted by law, each holder of Restricted Securities,
its officers, partners and directors and each person, if any, who controls any
such holder within the meaning of the Securities Act or the Exchange Act in the
same manner and to the same extent as the Corporation is required to indemnify a
seller of Restricted Shares in Section 3.9 hereof. If, in connection with any
such registration statement, any holder of Restricted Securities shall furnish
written information to the Corporation expressly for use in the registration
statement, then such holder shall indemnify the Corporation, each director of
the Corporation, each officer of the Corporation who signs such registration
statement and each person, if any, who controls the Corporation within the
meaning of the Securities Act to the same extent as a seller of Restricted
Shares is required to indemnify such persons in Section 3.9 hereof.

     SECTION 5. ELECTION OF DIRECTORS.

          5.1   VOTING FOR DIRECTORS. At each annual meeting of the stockholders
of the Corporation and at each special meeting of the stockholders of the
Corporation called for the purposes of electing directors of the Corporation,
and at any time at which stockholders of the Corporation shall have the right
to, or shall, vote for the election of directors, then, in each such event, each
Investor holding Series Preferred Shares shall vote all Series Preferred Shares
and
                                     - 26 -
<Page>

any other shares of voting stock of the Corporation then owned or controlled as
to voting rights) by it, whether by purchase, exercise of rights, warrants or
options, stock dividends or otherwise:

                (a)  to fix and maintain the number of directors on the Board of
Directors of the Corporation at not more than seven (7);

                (b)  pursuant to Paragraph A.6(b)(i) of Article III of the
Certificate, to elect to the Board:

                     (i)   one (1) director designated by HCV III, HCV IV and
HCV V, who shall initially be John W. Littlechild;

                     (ii)  one (1) director designated by HCV VI, who shall
initially be Robert S. Cohen;

                     (iii) one (1) director designated by Rho Management Trust
II;

                     (iv)  one (1) director designated by Rho Ventures IV (QP),
L.P. ("Rho Management"), who shall initially be Mark Leschly;

                     (v)   one (1) director designated by Johnson & Johnson
Development Corporation, who shall initially be Roger Guidi; and

                (c)  to elect two (2) directors designated by the Company, one
of which shall be the Chief Executive Officer, and one of which shall initially
be Zola Horovitz.

          5.2   COOPERATION OF THE CORPORATION. The Corporation shall use its
best efforts to effectuate the purposes of this Section 5, including promoting
the adoption of any necessary amendment of the By-laws of the Corporation and
the Certificate.

          5.3   NOTICES. The Corporation shall provide the Investors with at
least twenty (20) days' prior notice in writing of any intended mailing of
notice to the stockholders of the Corporation for a meeting at which directors
are to be elected. The Investors shall notify the Corporation in writing at
least three (3) days prior to such mailing of the persons designated by them
pursuant to Paragraph A.6(b) (i) of Article III of the Certificate and Section
5.1 above as nominees for election to the Board. In the absence of any notice
from the applicable Investors, the director(s) then serving and previously
designated by such applicable Investors shall be renominated.

          5.4   REMOVAL. Except as otherwise provided in this Section 5, no
Investor shall vote to remove any member of the Board designated in accordance
with the foregoing provisions of this Section 5 unless the party who designated
such director (the "Designating Party") shall so vote or otherwise consent, and,
if the Designating Party shall so vote or otherwise consent, then the
non-designating Investors shall likewise so vote. Any vacancy on the Board
created by the resignation, removal, incapacity or death of any person
designated under Section 5.1 shall be filled by another person designated by the
original Designating Party. Each Investor shall vote all voting Series Preferred
Shares of the Corporation and all other shares

                                     - 27 -
<Page>

of voting stock of the Corporation owned or controlled by such Investor in
accordance with each such new designation, and no such vacancy shall be filled
in the absence of a new designation by the original Designating Party.

          5.5   ADDITIONAL RIGHTS. The member of the Board designated by Rho
Management shall have the right to be a member of the Compensation Committee or
similar committee created by the Board. In the event that Rho Management does
not elect to designate a member of the Board, it shall be entitled to receive
notices of all Board meetings and have an observer attend all meetings of the
Board and committees thereof.

          5.6   DURATION OF SECTION. This Section 5 and the rights and
obligations of the parties hereunder shall automatically terminate on the first
to occur of December 31, 2007 or the closing of an Initial Public Offering (the
"Expiration Date"). Prior to such termination the rights and obligations of any
Investor under this Section 5 shall terminate upon the date on which such
Investor no longer owns any Restricted Securities, whereupon the obligations of
the remaining Investors to vote in favor of the designee of such Investor shall
also terminate.

     SECTION 6. REMEDIES. In case any one or more of the covenants and/or
agreements set forth in this Agreement shall have been breached by any party
hereto, the party or parties entitled to the benefit of such covenants or
agreements may proceed to protect and enforce its or their rights, either by
suit in equity and/or action at law, including, but not limited to, an action
for damages as a result of any such breach and/or an action for specific
performance of any such covenant or agreement contained in this Agreement.
Notwithstanding the generality of the foregoing, in the event that the
Corporation breaches any of its covenants and/or agreements set forth herein,
the Investors shall have the additional remedy, in their sole discretion upon
the election by a majority in voting power thereof, provided that such breach
has not been cured by the 60th day after receipt of notice from an Investor of
such breach by the Corporation, to exercise immediately their right of
redemption set forth in Article III, Section A.5 of the Certificate, as provided
therein with respect to all, but not less than all, of their shares,
irrespective of whether such right of redemption otherwise is mature. With
respect to a breach of which the Corporation is aware or reasonably should be
aware, such 60 day period within which the Corporation shall have the right to
cure such breach shall be deemed to have commenced on the tenth day after the
occurrence of such breach, irrespective of notice of such breach from an
Investor, if the Corporation shall not have notified the Investors of such
breach by such date. The rights, powers and remedies of the parties under this
Agreement are cumulative and not exclusive of any other right, power or remedy
which such parties may have under any other agreement or law. No single or
partial assertion or exercise of any right, power or remedy of a party hereunder
shall preclude any other or further assertion or exercise thereof.

     SECTION 7. SUCCESSORS AND ASSIGNS. Except as otherwise expressly provided
herein, this Agreement shall bind and inure to the benefit of the Corporation,
BWH, each of the Investors, the Management Holders and the respective successors
and assigns of the Corporation, BWH, each of the Investors and the Management
Holders. Subject to the requirements of Section 3 hereof, this Agreement and the
rights and duties of the Investors set forth herein may be freely assigned, in
whole or in part, by each Investor. Rights under Section 3 may be transferred
only to an Investor or to a person or entity which acquires at least 100,000
Restricted

                                     - 28 -
<Page>

Shares, and, in either case, any such transferee shall, as a condition to such
transfer, deliver to the Corporation a written instrument by which such
transferee identifies itself, gives the Corporation notice of the transfer of
such rights, identifies the securities of the Corporation owned or acquired by
it and agrees to be bound by the obligations imposed hereunder to the same
extent as if such transferee were an Investor hereunder. A transferee to whom
rights are transferred pursuant to this Section 7 will be thereafter deemed to
be an Investor for the purpose of the execution of such transferred rights and
may not again transfer such rights to any other person or entity, other than as
provided in this Section 7. Neither this Agreement nor any of the rights or
duties of the Corporation or BWH set forth herein shall be assigned by the
Corporation or BWH, as the case may be, in whole or in part, without having
first received the written consent of the Investors holding sixty-six and
two-thirds percent (66 2/3%) in voting power of the outstanding Series Preferred
Shares, determined in accordance with Section A.6(a) of the certificate
(including, in such calculation, any outstanding Restricted Shares by such
Investors).

     SECTION 8. DURATION OF AGREEMENT. The rights and obligations of the
Corporation, BWH, each Investor and each Management Holder set forth herein
shall survive indefinitely, unless and until, by their respective terms, they
are no longer applicable.

     SECTION 9. ENTIRE AGREEMENT. This Agreement, together with the other
writings referred to herein or delivered pursuant hereto which form a part
hereof, contains the entire agreement among the parties with respect to the
subject matter hereof and amends, restates and supersedes all prior and
contemporaneous arrangements or understandings with respect thereto; PROVIDED,
HOWEVER, that the provisions of the Research and License Agreement effective
August 1, 1992, as amended November 22, 1996, between the Corporation and BWH
(other than Section 8.9 thereof which is superseded in its entirety by this
Agreement and the Stock Restriction Agreement dated December 3, 1993 between the
Corporation and BWH) shall continue in full force and effect.

     SECTION 10. NOTICES. All notices, requests, consents and other
communications hereunder to any party shall be deemed to be sufficient if
contained in a written instrument delivered in person or duly sent by first
class registered, certified or overnight mail, postage prepaid, or telecopied
with a confirmation copy by regular mail, addressed or telecopied, as the case
may be, to such party at the address or telecopier number, as the case may be,
set forth below or such other address or telecopier number, as the case may be,
as may hereafter be designated in writing by the addressee to the addressor
listing all parties:

                     (i)    If to the Corporation, to:

                            NitroMed, Inc.
                            12 Oak Park Drive
                            Bedford, MA 01730
                            Attention:  Chief Executive Officer
                            Telecopier: (617) 275-2282

                                     - 29 -
<Page>

                            with a copy to:

                            Hale and Dorr LLP
                            60 State Street
                            Boston, MA 02109
                            Attention:  Steven D. Singer, Esq.
                            Telecopier: (617) 526-5000

                     (ii)   If to the Investors, as set forth on Schedule 1.

                            with a copy to:

                            Law Office of Gregory F.W. Todd
                            888 Seventh Avenue, Suite 4500
                            New York, NY 10019
                            Attention:  Gregory F.W. Todd, Esq.
                            Telecopier: (212) 246-5454

                     (iii)  If to BWH, to:

                            The Brigham and Women's Hospital
                            75 Francis Street
                            Boston, MA 02115
                            Attention: Dr. Vandana D. Yajnick

                            with a copy to:

                            Brigham and Women's Medical Center, Inc.
                            10 Vining Street
                            Boston, MA 02115
                            Attention: Office of General Counsel

                     (iv)   If to the Management Holders, as set forth on
                            Schedule 2.

     All such notices, requests, consents and communications shall be deemed to
have been received (a) in the case of personal delivery, on the date of such
delivery, (b) in the case of mailing, on the third business day following the
date of such mailing, (c) in the case of overnight mail, on the first business
day following the date of such mailing, and (d) in the case of facsimile
transmission, when confirmed by facsimile machine report.

     SECTION 11. CHANGES. The terms and provisions of this Agreement may not be
modified or amended, or any of the provisions hereof waived, temporarily or
permanently, except pursuant to the written consent of the Corporation and the
holders of at least sixty-five percent (65%) in voting power of the Series
Preferred Shares then outstanding, determined in accordance with Section A.6(a)
of Article III of the Certificate (including, in such calculation, any
outstanding Restricted Shares held by such holders); PROVIDED THAT no such
amendment may

                                     - 30 -
<Page>

reduce or materially adversely affect the rights of BWH or the Management
Holders without the consent of BWH or Management Holders holding a majority in
voting power of all Restricted Shares held by all Management Holders..

     SECTION 12. ADDITIONAL INVESTORS. Persons or entities that, after the date
hereof, purchase Series E Preferred Shares pursuant to the Series E Stock
Purchase Agreement and become "Investors" thereunder may, with the prior written
approval of the Corporation (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
"Investors" and "Series E Investors" for all purposes of this Agreement.

     SECTION 13. COUNTERPARTS. This Agreement may be executed in any number of
counterparts, and each such counterpart shall be deemed to be an original
instrument, but all such counterparts together shall constitute but one
agreement.

     SECTION 14. HEADINGS. The headings of the various sections of this
Agreement have been inserted for convenience of reference only and shall not be
deemed to be a part of this Agreement.

     SECTION 15. NOUNS AND PRONOUNS. Whenever the context may require, any
pronouns used herein shall include the corresponding masculine, feminine or
neuter forms, and the singular form of names and pronouns shall include the
plural and vice-versa.

     SECTION 16. SEVERABILITY. Any provision of this Agreement that is
prohibited or unenforceable in any jurisdiction shall, as to such jurisdiction,
be ineffective to the extent of such prohibition or unenforceability without
invalidating the remaining provisions hereof, and any such prohibition or
unenforceability in any jurisdiction shall not invalidate or render
unenforceable such provision in any other jurisdiction.

     SECTION 17. GOVERNING LAW. This Agreement shall be governed by and
construed in accordance with the laws of the State of Delaware, excluding the
conflict of law doctrines of Delaware or any other jurisdiction to the contrary.

     SECTION 18. EFFECTIVENESS. Notwithstanding any other provision of this
Agreement, this Agreement shall not be effective until the Closing (as such term
is defined in the Series D Stock Purchase Agreement).

     SECTION 19. TERMINATION OF AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT.
Notwithstanding anything to the contrary contained in the Old Stockholders'
Agreement, the Old Stockholders' Agreement is hereby terminated in its entirety
and superseded by the terms and conditions of this Agreement.

                  [Remainder of Page Left Intentionally Blank]

                                     - 31 -
<Page>

     IN WITNESS WHEREOF the parties hereto have executed this Fourth Amended and
Restated Stockholders' Agreement on the date first above written.

                            NITROMED, INC.

                            By:  /s/ Michael D. Loberg
                               -----------------------------------------
                                 Title: Chief Executive Officer

                            HEALTHCARE VENTURES III, L.P.

                            By:  HealthCare Partners III, L.P.,
                                 as General Partner

                            By:  /s/ John Littlechild
                               -----------------------------------------
                                 Title: General Partner

                            HEALTHCARE VENTURES IV, L. P.

                            By:  HealthCare Partners IV, L. P.,
                                 as General Partner

                            By:  /s/ John Littlechild
                               -----------------------------------------
                                 Title: General Partner

                            HEALTHCARE VENTURES V, L. P.

                            By:   HealthCare Partners V, L. P.,
                                  as General Partner

                            By:   /s/ John Littlechild
                               -----------------------------------------
                                 Title: General Partner

                            HEALTHCARE VENTURES VI, L.P.

                            By:   HealthCare Partners VI, L.P.,
                                  as General Partner

                            By:   /s/ John Littlechild
                               -----------------------------------------
                                 Title: General Partner

                                     - 32 -
<Page>

[Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            RHO MANAGEMENT TRUST II

                            By:  Rho Management Company, Inc.,
                                 as Investment Adviser

                            By:  /s/ Mark Leschly
                               -----------------------------------------
                                 Title: Managing Director

                            RHO VENTURES IV, L.P.

                            By:  Rho Management Ventures IV, L.L.C.,
                                 as General Partner

                            By:  /s/ Mark Leschly
                               -----------------------------------------
                                 Title: Managing Director

                            RHO VENTURES IV GmbH & CO.
                            BETEILIGUNGS KG

                            By:  Rho Capital Partners Verwaltungs GmbH,
                                 as General Partner

                            By:  /s/ Mark Leschly
                               -----------------------------------------
                                 Title: Managing Director

                            RHO VENTURES IV (QP), L.P.

                            By:  Rho Management Ventures IV, L.L.C.,
                                 as General Partner

                            By:  /s/ Mark Leschly
                               ----------------------------------------
                                 Title: Managing Director

                                     - 33 -
<Page>

     [Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            ATLAS VENTURE FUND II, L.P.

                            By:  Atlas Venture Associates II,
                                 L.P., as General Partner

                            By:  /s/ illegible
                               -----------------------------------------
                                 Title: General Partner

                            M & G EQUITIES, INC.

                            By:  /s/ Michael Karfunkel
                               -----------------------------------------
                                 Title: President

                            HUDSON TRUST

                            By:  /s/ Scott M. Ciccone
                               -----------------------------------------
                                 Title: Trustee

                            THE GOLDMAN SACHS GROUP, INC.

                            By:  /s/ Eric M. Mindich
                               -----------------------------------------
                                 Name: Eric M. Mindich
                                 Title: Vice President

                            *THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

                            By:  /s/ Brian N. Hicks
                               -----------------------------------------
                                 Name: Brian N. Hicks
                                 Title: Director, Corporate Sponsored
                                        Research and Licensing

----------
*    Except with respect to Sections 2.2, 2.4 through 2.14, 3.1 through 3.4, 3.6
and 5.1 through 5.5. of the Agreement, under which BWH has no rights,
liabilities or responsibilities.

                                     - 34 -
<Page>

     [Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            B.U.N.P.

                            By:  /s/ illegible
                               -----------------------------------------
                                  Name:
                                  Title: Partner-B.U.N.P.

                            JOHNSON AND JOHNSON DEVELOPMENT
                            CORPORATION

                            By:  /s/ Roger J. Guidi
                               -----------------------------------------
                                  Name: Roger J. Guidi
                                  Title: Vice President

                            CURRAN PARTNERS L.P.

                            By:  /s/ John P. Curran
                               -----------------------------------------
                                  Name:  John P. Curran
                                  Title: General Partner

                            DELAWARE CHARTER AND TRUST
                            JOHN P. CURRAN IRA

                            By:  /s/ John P. Curran
                               -----------------------------------------
                                  Name:  John P. Curran
                                  Title: Self Directed IRA

                            SENTRON MEDICAL, INC.

                            By:
                               -----------------------------------------
                                  Name:
                                  Title:

                                     - 35 -
<Page>

     [Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            LOMBARD ODIER & CIE

                            By:  /s/ Alexandre Meyer   /s/ Fernando Perez Diaz
                               -----------------------------------------------
                                 Name: Alexandre Meyer     Fernando Perez Diaz
                                 Title: Vice President     Assistant Manager

                            BANK JULUIS BAER & CO. LTD.

                            By:  /s/ illegible
                               ---------------------------------------------
                                   Name:
                                   Title: Vice President

                            AETNA LIFE INSURANCE COMPANY

                            By:
                               ---------------------------------------------
                                   Name:
                                   Title:

                            MYTHEN TREUHAND & VERWALTUNGS AG

                            By:  /s/ Alex Fancelli
                               ---------------------------------------------
                                   Title: Alex Fancelli
                                          CEO

                            BANK SARASIN & CO.

                            By:
                               ---------------------------------------------
                                   Name:
                                   Title:

                            GZB BANK (SCHWEIZ) AG

                            By:
                               ---------------------------------------------
                                   Name:
                                   Title:

                                     - 36 -
<Page>

     [Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            ---------------------------------------------
                            Heinrich Hasler

                            CC/M NITROMED HOLDINGS, L.P.

                            By:  /s/ David R. Ramsay
                               ------------------------------------------
                            Name:
                            Title:

                            CC NITROMED HOLDINGS, L.P.

                            By:  /s/ David R. Ramsay
                               ------------------------------------------
                            Name:
                            Title:

                            CC/Q PARTNERS, L.P.

                            By:  /s/ David R. Ramsay
                               ------------------------------------------
                            Name:
                            Title:

                            DC 1998 NFA TRUST

                            By:  /s/ Lee Casty
                               ------------------------------------------
                                   Name:  Lee Casty
                                   Title: Trustee

                            /s/ James M. Casty
                            ---------------------------------------------
                            James M. Casty

                            /s/ Lawrence Abrams
                            ---------------------------------------------
                            Lawrence Abrams

                                     - 37 -
<Page>

     [Signature Page to Fourth Amended and Restated Stockholders' Agreement]

                            /s/ Robert Granovsky
                            ---------------------------------------------
                            Robert Granovsky

                            /s/ Manuel Worcel
                            ---------------------------------------------
                            **Manuel Worcel

                            /s/ Michael D. Loberg
                            ---------------------------------------------
                            **Michael D. Loberg

                            /s/ Joseph M. Grimm
                            ---------------------------------------------
                            **Joseph M. Grimm

                            /s/ L. Gordon Letts
                            ---------------------------------------------
                            **L. Gordon Letts

----------
**      Except with respect to Sections 2, 3.1 through 3.4, 3.6 and 5 hereof,
under which the signatory has no rights, liabilities or responsibilities.

                                     - 38 -
<Page>

                                   SCHEDULE 1

HealthCare Ventures III, L.P.
HealthCare Ventures IV, L.P.
HealthCare Ventures V, L.P.
HealthCare Ventures VI, L.P.
44 Nassau Street, Second Floor
Princeton, NJ 08543
Attn: Jeffrey Steinberg

Atlas Venture Fund II, L.P.
222 Berkeley Street
Boston, MA 02116
Attn: Jean-Francois Formela

Rho Management Trust II
Rho Ventures IV, L.P.
Rho Ventures IV GmbH & Co. Beteiligungs KG
Rho Ventures IV (QP), L.P.
c/o Rho Management Co., Inc.
152 W. 57th Street, 23rd Floor
New York, NY 10019
Attn: Chief Financial Officer

Hudson Trust
47 Hulfish Street
Princeton, NJ 08542
Attn: Thomas O'Dougherty

Lawrence Abrams
24 Central Park South
New York, NY 10019

M&G Equities, Inc.
c/o American Stock Transfer & Trust Co.
40 Wall Street
New York, NY 10005
Attn: Michael Karfunkel

The Brigham and
Women's Hospital, Inc.
75 Francis Street
Boston, MA 02115
Attn: Vandana D. Yajnick, Ph.D.

                                     - 39 -
<Page>

Johnson & Johnson Development Corporation
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
Attn: Roger Guidi

Aetna Life Insurance Company
151 Farmington Avenue, RC21
Hartford, CT 06156-9000
Attn: David M. Clarke
       IG6U Private Equity Group

The Goldman Sachs Group, Inc.
85 Broad Street, 12th Floor
New York, NY 10004

B.U.N.P
c/o Boston University
Community Technology Fund
108 Bay State Road
Boston, MA 02215
Attn: Matthew Burns or Matthew Crowley

Curran Partners L.P.
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Delaware Charter and Trust
John P. Curran IRA
c/o Curran Capital Management
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Sentron Medical, Inc.
4445 Lake Forest Drive, Suite 600
Cincinnati, OH 45242
Attn: Dennis B. Costello
       Group Director, Venture Projects

Lombard Odier & Cie
Toedistr.36
8002 Zurich
Switzerland
Attn: Alexandre Meyer

                                     - 40 -
<Page>

Bank Juluis Baer & Co. Ltd.
Bahnhofstr. 36
8001 Zurich
Switzerland
Attn: Claudio Studer

Mythen Treuhand & Verwaltungs AG
Splugenstrasse 9
8002 Zurich
Switzerland
Attn: Alex Fancelli

Robert Granovsky
c/o The Goldman Sachs Group
One New York Plaza
50th Floor
New York, NY 10004

Bank Sarasin & Co.
Elisabethenstrasse 62
CH-4002 Basel
Switzerland

GZB Bank (Schweiz) AG
Talacker 42
Zurich, Ch-8022
Switzerland

Heinrich Hasler
Nidelbadstr 90
Zurich, 8038
Switzerland

CC/M NitroMed Holdings, L.P.
CC NitroMed Holdings, L.P.
CC/Q Partners, L.P.
c/o Care Capital LLC
Princeton Overlook One
100 Overlook Center & Route 1
Princeton, NJ 08540

DC 1998 NFA Trust
c/o IFX Corporation
Venture American Securities
707 Skokie Boulevard, Suite 580
Northbrook, IL 60062

                                     - 41 -
<Page>

James M. Casty
6185 Northwest Way
Boca Raton, FL 33496

                                     - 42 -
<Page>

                                   SCHEDULE 2

Manuel Worcel
c/o NitroMed, Inc.
12 Oak Park Drive
Bedford, Massachusetts 01730

Michael D. Loberg
c/o NitroMed, Inc.
12 Oak Park Drive
Bedford, Massachusetts 01730

Joseph M. Grimm
c/o NitroMed, Inc.
12 Oak Park Drive
Bedford, Massachusetts 01730

L. Gordon Letts
c/o NitroMed, Inc.
12 Oak Park Drive
Bedford, Massachusetts 01730

                                     - 43 -
<Page>

                                    EXHIBIT A

                       Form of Stock Restriction Agreement

                                     - 44 -
<Page>

                           AMENDMENT NO. 1 AND WAIVER
                                       TO
               FOURTH AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT

     This Amendment No. 1 and Waiver dated November 20, 2001 (the "Amendment")
to the Fourth Amended and Restated Stockholders' Agreement dated May 22, 2001
(the "Agreement") by and among NitroMed, Inc., a Delaware corporation (the
"Corporation"), the stockholders of the Corporation listed on SCHEDULE 1 thereto
(the "Investors"), the individuals listed on SCHEDULE 2 thereto and The Brigham
and Women's Hospital, Inc., is entered into by the Corporation and the
undersigned Investors representing at least 65% in voting power of the
outstanding Series Preferred Shares. Except as set forth below, the Agreement
shall remain in full force and effect. Capitalized terms used herein and not
otherwise defined shall have the meanings assigned to them in the Agreement.

     WHEREAS, the Corporation intends to issue and sell 250,000 shares of Series
F Junior Convertible Preferred Stock, $.01 par value per share, of the
Corporation ("Series F Preferred Stock") to Boston Scientific Corporation, a
Delaware corporation ("Boston Scientific"), pursuant to a Series F Junior
Convertible Preferred Stock Purchase Agreement dated the date hereof; and

     WHEREAS, the Corporation and the undersigned Investors desire to amend the
Agreement such that, among other things, Boston Scientific shall be made a party
thereto.

     NOW, THEREFORE, in consideration of the mutual covenants and agreements
contained herein, the receipt and sufficiency of which are hereby acknowledged,
the parties hereto agree as follows:

1.   AMENDMENTS TO THE AGREEMENT. Acting in accordance with Section 11 of the
Agreement, the Agreement is hereby amended as follows:

     (a)  SCHEDULE 1 of the Agreement is hereby amended and restated in its
entirety, as set forth on EXHIBIT A attached hereto, pursuant to which Boston
Scientific is added to SCHEDULE 1 of the Agreement and thereby is deemed an
"Investor" as such term is defined in the Agreement, subject to all of the
terms, conditions, benefits, rights, limitations and restrictions applicable to
Investors set forth therein.

     (b)  Section 1 is hereby amended to:

          (i)     restate the definition of "Excluded Securities" to read in its
entirety as follows:

                  EXCLUDED SECURITIES shall mean, collectively:

                      (i)   the Reserved Shares;

<Page>

                      (ii)  Common Stock issued or issuable to officers,
          directors or employees of or consultants or independent contractors to
          the Corporation, pursuant to any written agreement, plan or
          arrangement, including pursuant to any options granted under the 1993
          Equity Incentive Plan of the Corporation (the "1993 Equity Incentive
          Plan"), to purchase, or rights to subscribe for, such Common Stock,
          that is set forth on Schedule 5.2 of the Series F Stock Purchase
          Agreement or that has been approved in form and in substance by the
          holders of a majority of the combined voting power of the Series
          Preferred Shares then outstanding, calculated in accordance with
          Section A.6(a) of Article III of the Certificate (including, in such
          calculation, any outstanding Restricted Shares held by such holders),
          and which, as a condition precedent to the issuance of such shares,
          provides for the vesting of such shares and subjects such shares to
          restrictions on transfers and rights of first offer in favor of the
          Corporation that have been approved by the holders of a majority of
          the combined voting power of the Series Preferred Shares then
          outstanding, calculated in accordance with Section A.6(a) of Article
          III of the Certificate (including, in such calculation, any
          outstanding Restricted Shares held by such holders), (collectively,
          the "Required Terms"), unless any of such Required Terms are waived by
          holders at least a majority of the voting power of the Series
          Preferred Shares then outstanding (determined as set forth in Section
          A.6(a) of the Certificate); PROVIDED, HOWEVER, that the maximum number
          of shares of Common Stock hereafter issuable pursuant to the 1993
          Equity Incentive Plan and all such agreements, plans and arrangements
          shall not exceed 2,288,200 shares (subject to adjustment as required
          to comply with any anti-dilution rights set forth in any such
          agreement, plan or arrangement);

                      (iii) Common Stock issued as a stock dividend payable in
          shares of Common Stock, or capital stock of any class issuable upon
          any subdivision, recombination, split-up or reverse stock split of all
          the outstanding shares of such class of capital stock of the
          Corporation;

                      (iv)  any securities issued pursuant to the acquisition by
          the Corporation of any other corporation, partnership, joint venture,
          trust or other entity by any merger, stock acquisition,
          reorganization, purchase of substantially all assets or otherwise in
          which the Corporation, or its stockholders of record immediately prior
          to the effective date of such transaction, directly or indirectly, own
          at least a majority of the voting power of the acquired entity or the
          resulting entity after such transaction; and

                      (v)   any shares of Common Stock, Preferred Stock or any
          other security convertible into or exercisable or exchangeable for
          Common Stock or Preferred Stock issued to banks or leasing companies
          in order to obtain financing or to secure leases of equipment; and

                      (vi)  a maximum of 516,364 shares of Common Stock (subject
          to adjustment) issued or issuable upon the exercise of the 1994 Bridge
          Warrants,

                                      - 2 -
<Page>

          1995 Bridge Warrants, 1996 Bridge Warrants and the 1994 Capital
          Support Warrants.

          (ii)    restate the definition of "Series Preferred Shares" to read in
its entirety as follows:

                  SERIES PREFERRED SHARES shall mean collectively the Series A
          Preferred Shares, Series B Preferred Shares, Series C Preferred
          Shares, Series D Preferred Shares, Series E Preferred Shares and
          Series F Preferred Shares.

          (iii)   add the following definitions:

                  SERIES F INVESTOR shall mean the holder of the Corporation's
          Series F Preferred Stock.

                  SERIES F PREFERRED SHARES shall mean shares of Series F
          Preferred Stock issued or issuable pursuant to the Series F Stock
          Purchase Agreement.

                  SERIES F PREFERRED STOCK shall mean Series F Junior
          Convertible Preferred Stock, par value $.01 per share, of the
          Corporation.

                  SERIES F STOCK PURCHASE AGREEMENT shall mean the Series F
          Junior Convertible Preferred Stock Purchase Agreement dated as of
          November 20, 2001, as it may be amended from time to time, between the
          Corporation and the Series F Investor.

          (c)     Section 12 shall be deleted in its entirety and a new Section
12 shall be inserted in lieu thereof which shall read as follows:

                  SECTION  12. ADDITIONAL INVESTORS. Any person or entity that,
          on or after the date hereof, purchases Series F Preferred Shares
          pursuant to the Series F Stock Purchase Agreement and becomes an
          "Investor" thereunder may, with the prior written approval of the
          Corporation (but without the need for approval by any other party to
          this Agreement), become a party to this Agreement by executing and
          delivering a counterpart signature page hereto, whereupon such person
          or entity shall be deemed an "Investor" and "Series F Investor" for
          all purposes of this Agreement.

2.   WAIVER. Acting in accordance with Section 11 of the Agreement, the
undersigned hereby waive the Investors' rights of first refusal and of prior
notice under Section 2.3 of the Agreement with respect to the issuance by the
Corporation of the Series F Preferred Stock to Boston Scientific and the shares
of Common Stock issuable upon conversion of such shares of Series F Preferred
Stock.

3.   The Agreement, as supplemented and modified by this Amendment, together
with the other writings referred to in the Agreement or delivered pursuant
thereto which form a part thereof, contains the entire agreement among the
parties with respect to the subject matter

                                      - 3 -
<Page>

thereof and amends, restates and supersedes all prior and contemporaneous
arrangements or understandings with respect thereto.

4.   Upon the effectiveness of this Amendment, on and after the date hereof,
each reference in the Agreement to "this Agreement," "hereunder," "hereof,"
"herein" or words of like import, and each reference in the other documents
entered into in connection with the Agreement, shall mean and be a reference to
the Agreement, as amended hereby. Except as specifically amended above, the
Agreement shall remain in full force and effect and is hereby ratified and
confirmed.

5.   This Amendment shall be governed by, and construed and enforced in
accordance with, the substantive laws of the State of Delaware without regard to
its principles of conflicts of laws.

6.   This Amendment may be executed in any number of counterparts, and each such
counterpart shall be deemed to be an original instrument, but all such
counterparts together shall constitute but one agreement.

         [The remainder of this page has intentionally been left blank.]

                                      - 4 -
<Page>

     IN WITNESS WHEREOF, The Corporation and each of the parties set forth on
the foregoing signature pages have caused this Amendment No. 1 and Waiver to
Fourth Amended and Restated Stockholders' Agreement to be executed as of the
date first above written.

                              NITROMED, INC.

                              By:   /s/ Michael D. Loberg
                                 ----------------------------------------------
                                  Name: Michael D. Loberg
                                  Title: CEO

                              HEALTHCARE VENTURES III, L.P.

                              By:   HealthCare Partners III, L.P.,
                                    as General Partner

                              By:   /s/ Jeffrey Steinberg
                                 ----------------------------------------------
                                    Title: General Partner

                              HEALTHCARE VENTURES IV, L. P.

                              By:   HealthCare Partners IV, L. P.,
                                    as General Partner

                              By:   /s/ Jeffrey Steinberg
                                 ----------------------------------------------
                                    Title: General Partner

                              HEALTHCARE VENTURES V, L. P.

                              By:   HealthCare Partners V, L. P.,
                                    as General Partner

                              By:   /s/ Jeffrey Steinberg
                                 ----------------------------------------------
                                   Title:  General Partner

<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              HEALTHCARE VENTURES VI, L.P.

                              By:   HealthCare Partners VI, L.P.,
                                    as General Partner

                              By:   /s/ Jeffrey Steinberg
                                 -----------------------------------------------
                                   Title: General Partner

                              RHO MANAGEMENT TRUST II

                              By:   Rho Management Company, Inc.,
                                    as Investment Adviser

                              By:
                                 -----------------------------------------------
                                    Title:

                              RHO VENTURES IV, L.P.

                              By:   Rho Management Ventures IV, L.L.C.,
                                    as General Partner

                              By:
                                 -----------------------------------------------
                                    Title:

                              RHO VENTURES IV GmbH & CO.
                              BETEILIGUNGS KG

                              By:   Rho Capital Partners Verwaltungs GmbH,
                                    as General Partner

                              By:
                                 -----------------------------------------------
                                    Title:

                                      - 6 -
<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              RHO VENTURES IV (QP), L.P.

                              By:   Rho Management Ventures IV, L.L.C.,
                                    as General Partner

                              By:   /s/ Mark Leschly
                                 -----------------------------------------------
                                    Title: Managing Member

                              ATLAS VENTURE FUND II, L.P.

                              By:   Atlas Venture Associates II,
                                    L.P., as General Partner

                              By:   /s/ illegible
                                 -----------------------------------------------
                                    Title: General Partner

                              M & G EQUITIES, INC.

                              By:
                                 -----------------------------------------------
                                    Title: President

                              HUDSON TRUST

                              By:   /s/ Scott M. Ciccone
                                 -----------------------------------------------
                                    Title: Trustee

                              THE GOLDMAN SACHS GROUP, INC.

                              By:   /s/ Eric M. Mindich
                                 -----------------------------------------------
                                    Name: Eric M. Mindich
                                    Title: Vice President, The Goldman Sachs
                                            Group Inc.

                                      - 7 -
<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              *THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

                              By:   /s/ Brian N. Hicks
                                 -----------------------------------------------
                                    Name: Brian N. Hicks
                                    Title: Corporate Sponsored Research and
                                           Licensing

                              B.U.N.P.

                              By:   /s/ illegible
                                 -----------------------------------------------
                                       Name:
                                       Title: Partner- B.U.N.P.

                              JOHNSON AND JOHNSON DEVELOPMENT
                              CORPORATION

                              By:   /s/ Roger J. Guidi
                                 -----------------------------------------------
                                       Name: Roger J. Guidi
                                       Title: Vice President

                              CURRAN PARTNERS L.P.

                              By:   /s/ John P. Curran
                                 -----------------------------------------------
                                       Name: John P. Curran
                                       Title: General Partner

                              DELAWARE CHARTER AND TRUST
                              JOHN P. CURRAN IRA

                              By:   /s/ John P. Curran
                                 -----------------------------------------------
                                       Name: John P. Curran
                                       Title: Self Directed IRA

----------
*    Except with respect to Sections 2.2, 2.4 through 2.14, 3.1 through 3.4, 3.6
and 5.1 through 5.5 of the Agreement, under which BWH has no rights, liabilities
or responsibilities.

                                      - 8 -
<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              SENTRON MEDICAL, INC.

                              By:   /s/ Vincent M. Paglino
                                 -----------------------------------------------
                                       Name: Vincent M. Paglino
                                       Title: Vice President

                              LOMBARD ODIER & CIE

                              By:   /s/ Tania Plage       /s/Fernando Perez Diaz
                                 -----------------------------------------------
                                    Name:  Tania Plage      Fernando Perez Diaz
                                    Title: Assistant Vice    Assistant Manager
                                            President

                              BANK JULUIS BAER & CO. LTD.

                              By:   /s/ Tobias Kaeser     /s/ Robert Kessler
                                 -----------------------------------------------
                                    Name:  Tobias Kaeser      Robert Kessler
                                    Title: VP                 Vice President

                              AETNA LIFE INSURANCE COMPANY

                              By:   /s/ David M. Clarke
                                 -----------------------------------------------
                                       Name: David M. Clarke
                                       Title: Investment Manager

                              MYTHEN TREUHAND & VERWALTUNGS AG

                              By:   /s/ Alex Fancelli
                                 -----------------------------------------------
                                       Title: Alex Fancelli/CEO

                              BANK SARASIN & CO.

                              By:
                                 -----------------------------------------------
                                       Name:
                                       Title:

                                      - 9 -
<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              GZB BANK (SCHWEIZ) AG

                              By:
                                 -----------------------------------------------
                                       Name:
                                       Title:

                              --------------------------------------------------
                              Heinrich Hasler

                              CC/M NITROMED HOLDINGS, L.P.

                              By:
                                 ----------------------------------------------
                              Name:
                              Title:

                              CC NITROMED HOLDINGS, L.P.

                              By:
                                 -----------------------------------------------
                              Name:
                              Title:

                              CC/Q PARTNERS, L.P.

                              By:
                                 -----------------------------------------------
                              Name:
                              Title:

                              DC 1998 NFA TRUST

                              By:   /s/ Lee Casty
                                 -----------------------------------------------
                                       Name:  Lee Casty
                                       Title: Trustee

                                     - 10 -
<Page>

                [Signature Page to Amendment No. 1 and waiver to
              Fourth Amended and Restated Stockholder's Agreement]

                              /s/ James M. Casty
                              --------------------------------------------------
                              James M. Casty

                              /s/ Lawrence Abrams
                              --------------------------------------------------
                              Lawrence Abrams

                              --------------------------------------------------
                              Robert Granovsky

                              /s/ Manuel Worcel
                              --------------------------------------------------
                              **Manuel Worcel

                              /s/ Michael D. Loberg
                              --------------------------------------------------
                              **Michael D. Loberg

                              /s/ Joseph M. Grimm
                              --------------------------------------------------
                              **Joseph M. Grimm

                              /s/ L. Gordon Letts
                              --------------------------------------------------
                              **L. Gordon Letts

----------
**   Except with respect to Sections 2, 3.1 through 3.4, 3.6 and 5 hereof, under
which the signatory has no rights, liabilities or responsibilities.

                                     - 11 -
<Page>

                                                                       EXHIBIT A

                                   SCHEDULE 1

HealthCare Ventures III, L.P.
HealthCare Ventures IV, L.P.
HealthCare Ventures V, L.P.
HealthCare Ventures VI, L.P.
44 Nassau Street, Second Floor
Princeton, NJ 08543
Attn: Jeffrey Steinberg

Atlas Venture Fund II, L.P.
222 Berkeley Street
Boston, MA 02116
Attn: Jean-Francois Formela

Rho Management Trust II
Rho Ventures IV, L.P.
Rho Ventures IV GmbH & Co. Beteiligungs KG
Rho Ventures IV (QP), L.P.
c/o Rho Management Co., Inc.
152 W. 57th Street, 23rd Floor
New York, NY 10019
Attn: Chief Financial Officer

Hudson Trust
47 Hulfish Street
Princeton, NJ 08542
Attn: Thomas O'Dougherty

Lawrence Abrams
24 Central Park South
New York, NY 10019

M&G Equities, Inc.
c/o American Stock Transfer & Trust Co.
40 Wall Street
New York, NY 10005
Attn: Michael Karfunkel

The Brigham and
Women's Hospital, Inc.
75 Francis Street
Boston, MA 02115
Attn: Vandana D. Yajnick, Ph.D.

<Page>

Johnson & Johnson Development Corporation
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
Attn: Roger Guidi

Aetna Life Insurance Company
151 Farmington Avenue, RC21
Hartford, CT 06156-9000
Attn: David M. Clarke
       IG6U Private Equity Group

The Goldman Sachs Group, Inc.
85 Broad Street, 12th Floor
New York, NY 10004

B.U.N.P
c/o Boston University
Community Technology Fund
108 Bay State Road
Boston, MA 02215
Attn: Matthew Burns or Matthew Crowley

Curran Partners L.P.
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Delaware Charter and Trust
John P. Curran IRA
c/o Curran Capital Management
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Sentron Medical, Inc.
4445 Lake Forest Drive, Suite 600
Cincinnati, OH 45242
Attn: Dennis B. Costello
       Group Director, Venture Projects

Lombard Odier & Cie
Toedistr.36
8002 Zurich
Switzerland
Attn: Alexandre Meyer

                                     - 13 -
<Page>

Bank Julius Baer & Co. Ltd.
Bahnhofstr. 36
8001 Zurich
Switzerland
Attn: Claudio Studer

Mythen Treuhand & Verwaltungs AG
Splugenstrasse 9
8002 Zurich
Switzerland
Attn: Alex Fancelli

Robert Granovsky
c/o The Goldman Sachs Group
One New York Plaza
50th Floor
New York, NY 10004

Bank Sarasin & Co.
Elisabethenstrasse 62
CH-4002 Basel
Switzerland

GZB Bank (Schweiz) AG
Talacker 42
Zurich, Ch-8022
Switzerland

Heinrich Hasler
Nidelbadstr 90
Zurich, 8038
Switzerland

CC/M NitroMed Holdings, L.P.
CC NitroMed Holdings, L.P.
CC/Q Partners, L.P.
c/o Care Capital LLC
Princeton Overlook One
100 Overlook Center & Route 1
Princeton, NJ 08540

DC 1998 NFA Trust
c/o IFX Corporation
Venture American Securities
707 Skokie Boulevard, Suite 580
Northbrook, IL 60062

                                     - 14 -
<Page>

James M. Casty
6185 Northwest Way
Boca Raton, FL 33496

Boston Scientific Corporation
One Boston Scientific Place
Natick, MA 01760-1537

                                     - 15 -
<Page>

                                 AMENDMENT NO. 2
                                       TO
               FOURTH AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT

     This Amendment No. 2 dated May 12, 2003 (the "Amendment") to the Fourth
Amended and Restated Stockholders' Agreement dated May 22, 2001, as amended on
November 20, 2001 (the "Agreement"), by and among NitroMed, Inc., a Delaware
corporation (the "Corporation"), the stockholders of the Corporation listed on
SCHEDULE 1 thereto (the "Investors"), the individuals listed on SCHEDULE 2
thereto and The Brigham and Women's Hospital, Inc., is entered into by the
Corporation and the undersigned Investors representing at least 65% in voting
power of the outstanding Series Preferred Shares. Except as set forth below, the
Agreement shall remain in full force and effect. Capitalized terms used herein
and not otherwise defined shall have the meanings assigned to them in the
Agreement.

     WHEREAS, the Corporation and the undersigned Investors desire to amend the
Agreement such that each Investor holding Series Preferred Shares shall not be
obligated to vote to elect to the Board a director designated by Johnson &
Johnson Development Corporation; and

     WHEREAS, the Corporation and the undersigned Investors desire to further
amend the Agreement such that each Investor holding Series Preferred Shares
shall be obligated to vote to elect to the Board an additional director
designated by the Corporation and approved by at least a majority of the
directors on the Board of Directors of the Corporation, including the director
designated by HCV III, HCV IV and HCV V and the director designated by Rho
Ventures IV (QP), L.P.

     NOW, THEREFORE, in consideration of the mutual covenants and agreements
contained herein, the receipt and sufficiency of which are hereby acknowledged,
the parties hereto agree as follows:

1.   AMENDMENTS TO THE AGREEMENT. Acting in accordance with Section 11 of the
Agreement, the Agreement is hereby amended as follows:

     (a)  Section 1 is hereby amended to restate paragraph (ii) of the
definition of "EXCLUDED SECURITIES" to read in its entirety as follows:

                    "(ii)   Common Stock issued or issuable to officers,
          directors or employees of or consultants or independent contractors to
          the Corporation, pursuant to any written agreement, plan or
          arrangement, including pursuant to any options granted under the 1993
          Equity Incentive Plan of the Corporation (the "1993 Equity Incentive
          Plan") or the 2003 Stock Incentive Plan of the Corporation (the "2003
          Stock Incentive Plan"), to purchase, or rights to subscribe for, such
          Common Stock that has been approved in form and in substance by the
          holders of a majority of the combined voting power of the Series
          Preferred Shares then outstanding, calculated in accordance with
          Section A.6(a) of Article III of the Certificate (including, in such
          calculation, any outstanding Restricted Shares held by such holders),
          and which, as a condition precedent to the issuance of such

<Page>

          shares, provides for the vesting of such shares and subjects such
          shares to restrictions on transfers and rights of first offer in favor
          of the Corporation that have been approved by the holders of a
          majority of the combined voting power of the Series Preferred Shares
          then outstanding, calculated in accordance with Section A.6(a) of
          Article III of the Certificate (including, in such calculation, any
          outstanding Restricted Shares held by such holders), (collectively,
          the "Required Terms"), unless any of such Required Terms are waived by
          holders at least a majority of the voting power of the Series
          Preferred Shares then outstanding (determined as set forth in Section
          A.6(a) of the Certificate); PROVIDED, HOWEVER, that the maximum number
          of shares of Common Stock hereafter issuable pursuant to the 1993
          Equity Incentive Plan, the 2003 Stock Incentive Plan and all such
          agreements, plans and arrangements shall not exceed 3,088,200 shares
          (subject to adjustment as required to comply with any anti-dilution
          rights set forth in any such agreement, plan or arrangement);"

     (b)  Section 5.1(b)(v) shall be deleted in its entirety.

     (c)  Section 5.1(c) shall be deleted in its entirety and a new Section
5.1(c) shall be inserted in lieu thereof which shall read as follows:

                    "(c)    to elect three (3) directors designated by the
          Corporation, one of which shall be the Chief Executive Officer, one of
          which shall initially be Zola Horovitz, and one of which shall be
          subject to approval by at least a majority of the directors on the
          Board of Directors of the Corporation, including the approval of the
          director designated by HCV III, HCV IV and HCV V and the director
          designated by Rho Ventures IV (QP), L.P."

2.   The Agreement, as supplemented and modified by this Amendment, together
with the other writings referred to in the Agreement or delivered pursuant
thereto which form a part thereof, contains the entire agreement among the
parties with respect to the subject matter thereof and amends, restates and
supersedes all prior and contemporaneous arrangements or understandings with
respect thereto.

3.   Upon the effectiveness of this Amendment, on and after the date hereof,
each reference in the Agreement to "this Agreement," "hereunder," "hereof,"
"herein" or words of like import, and each reference in the other documents
entered into in connection with the Agreement, shall mean and be a reference to
the Agreement, as amended hereby. Except as specifically amended above, the
Agreement shall remain in full force and effect and is hereby ratified and
confirmed.

4.   This Amendment shall be governed by, and construed and enforced in
accordance with, the substantive laws of the State of Delaware without regard to
its principles of conflicts of laws.

5.   This Amendment may be executed in any number of counterparts, and each such
counterpart shall be deemed to be an original instrument, but all such
counterparts together shall constitute but one agreement.

           [The remainder of this page has intentionally been blank.]

                                      - 2 -
<Page>

     IN WITNESS WHEREOF, The Corporation and each of the parties set forth on
the foregoing signature pages have caused this Amendment No. 2 to Fourth Amended
and Restated Stockholders' Agreement to be executed as of the date first above
written.

                              NITROMED, INC.

                              By:   /s/ Michael D. Loberg
                                 -----------------------------------------
                                   Name: Michael D. Loberg
                                   Title: CEO

                              HEALTHCARE VENTURES III, L.P.

                              By:  HealthCare Partners III, L.P.,
                                   as General Partner

                              By:  /s/ Jeffrey Steinberg
                                 -----------------------------------------
                                   Title: General Partner

                              HEALTHCARE VENTURES IV, L.P.

                              By:  HealthCare Partners IV, L.P.,
                                   as General Partner

                              By:  /s/ Jeffrey Steinberg
                                 -----------------------------------------
                                   Title: General Partner

                              HEALTHCARE VENTURES V, L.P.

                              By:  HealthCare Partners V, L.P.,
                                   as General Partner

                              By:  /s/ Jeffrey Steinberg
                                 -----------------------------------------
                                  Title:  General Partner

<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              HEALTHCARE VENTURES VI, L.P.

                              By:  HealthCare Partners VI, L.P.,
                                   as General Partner

                              By   /s/ Jeffrey Steinberg
                                 -----------------------------------------
                                  Title:  General Partner

                              RHO MANAGEMENT TRUST II

                              By:  Rho Capital Partners, Inc.,
                                   as Investment Adviser

                              By:  /s/ Mark Leschly
                                 -----------------------------------------
                                   Title: Managing Partner

                              RHO VENTURES IV, L.P.

                              By:  Rho Management Ventures IV, L.L.C.,
                                   as General Partner

                              By:  /s/ Mark Leschly
                                 -----------------------------------------
                                   Title: Managing Member

                              RHO VENTURES IV GmbH & CO.
                              BETEILIGUNGS KG

                              By:  Rho Capital Partners Verwaltungs GmbH,
                                   as General Partner

                              By:  /s/ Mark Leschly
                                 -----------------------------------------
                                   Title: Managing Director

                                      - 4 -
<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              RHO VENTURES IV (QP), L.P.

                              By:  Rho Management Ventures IV, L.L.C.,
                                   as General Partner

                              By:  /s/ Mark Leschly
                                 -----------------------------------------
                                   Title: Managing Member

                              ATLAS VENTURE FUND II, L.P.

                              By:  Atlas Venture Associates II,
                                   L.P., as General Partner

                              By:  /s/ illegible
                                 -----------------------------------------
                                   Title: General Partner

                              M & G EQUITIES, INC.

                              By:
                                 -----------------------------------------
                                   Title: President

                              HUDSON TRUST

                              By:  /s/ Scott M. Ciccone
                                 -----------------------------------------
                                   Title: Trustee

                              THE GOLDMAN SACHS GROUP, INC.

                              By:
                                 -----------------------------------------
                                   Name:
                                   Title:

                                      - 5 -
<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              *THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

                              By:  /s/ Brian N. Hicks
                                 -----------------------------------------
                                   Name: Brian N. Hicks
                                   Title: Director, Corporate Sponsored
                                          Research and Licensing

                              B.U.N.P.

                              By:
                                 -----------------------------------------
                                   Name:
                                   Title:

                              JOHNSON AND JOHNSON DEVELOPMENT
                              CORPORATION

                              By:  /s/ Roger J. Guidi
                                 ------------------------------------
                                     Name: Roger J. Guidi
                                     Title: Vice President

                              CURRAN PARTNERS L.P.

                              By:
                                 -----------------------------------------
                                     Name:  John P. Curran
                                     Title: General Partner

                              DELAWARE CHARTER AND TRUST
                              JOHN P. CURRAN IRA

                              By:
                                 -----------------------------------------
                                     Name:  John P. Curran
                                     Title: Self Directed IRA

----------
*    Except with respect to Section 5.1 of the Agreement, under which BWH has
no rights, liabilities or responsibilities.

                                      - 6 -
<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              SENTRON MEDICAL, INC.

                              By:  /s/ Clifford C. Mentrup
                                 -----------------------------------------
                                     Name: Clifford C. Mentrup
                                     Title: General Counsel

                              LOMBARD ODIER & CIE

                              By:  /s/ Alexandre Meyer           /s/ Tania Plage
                                 -----------------------------------------------
                                   Name:  Alexandre Meyer        Tania Plage
                                   Title: Senior Vice President Assistant Vice
                                                                President

                              BANK JULUIS BAER & CO. LTD.

                              By:
                                 -----------------------------------------
                                     Name:
                                     Title:

                              AETNA LIFE INSURANCE COMPANY

                              By:
                                 -----------------------------------------
                                     Name:
                                     Title:

                              MYTHEN TREUHAND & VERWALTUNGS AG

                              By:
                                 -----------------------------------------
                                     Title:

                              BANK SARASIN & CO.

                              By:
                                 -----------------------------------------
                                     Name:
                                     Title:

                                      - 7 -
<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              GZB BANK (SCHWEIZ) AG

                              By:  /s/ Ursula Vollenweider
                                 -----------------------------------------
                                     Name:
                                     Title:

                              --------------------------------------------
                              Heinrich Hasler

                              CC/M NITROMED HOLDINGS, L.P.

                              By:  /s/ David R. Ramsay
                                 -----------------------------------------
                              Name:
                              Title:

                              CC NITROMED HOLDINGS, L.P.

                              By:  /s/ David R. Ramsay
                                 -----------------------------------------
                              Name:
                              Title:

                              CC/Q PARTNERS, L.P.

                              By:  /s/ David R. Ramsay
                                 -----------------------------------------
                              Name:
                              Title:

                              DC 1998 NFA TRUST

                              By:   /s/ Lee Casty
                                 -----------------------------------------
                                      Name: Lee Casty
                              Title:  Trustee

                              BOSTON SCIENTIFIC CORPORATION

                              By:
                                 -----------------------------------------
                                     Name:
                                     Title:

                                      - 8 -
<Page>

                      [Signature Page to Amendment No.2 to
              Fourth Amended and Restated Stockholder's Agreement]

                              /s/ James M. Casty
                              --------------------------------------------
                              James M. Casty

                              /s/ Lawrence Abrams
                              --------------------------------------------
                              Lawrence Abrams

                              /s/ Robert Granovsky
                              --------------------------------------------
                              Robert Granovsky

                              /s/ Manuel Sorcel
                              --------------------------------------------
                              **Manuel Worcel

                              /s/ Michael D. Loberg
                              --------------------------------------------
                              **Michael D. Loberg

                              /s/ Joseph M. Grimm
                              --------------------------------------------
                              **Joseph M. Grimm

                              --------------------------------------------
                              **L. Gordon Letts

----------
**    Except with respect to Section 5 hereof, under which the signatory has no
rights, liabilities or responsibilities.

                                      - 9 -
<Page>

                                 AMENDMENT NO. 3
                                       TO
               FOURTH AMENDED AND RESTATED STOCKHOLDERS' AGREEMENT

     This Amendment No. 3 dated July 31, 2003 (the "Amendment") to the Fourth
Amended and Restated Stockholders' Agreement dated May 22, 2001, as amended on
November 20, 2001 and May 12, 2003 (the "Agreement") by and among NitroMed,
Inc., a Delaware corporation (the "Corporation"), the stockholders of the
Corporation listed on SCHEDULE 1 thereto (the "Investors"), the individuals
listed on SCHEDULE 2 thereto and The Brigham and Women's Hospital, Inc., is
entered into by the Corporation and the undersigned Investors representing at
least 65% in voting power of the outstanding Series Preferred Shares. Except as
set forth below, the Agreement shall remain in full force and effect.
Capitalized terms used herein and not otherwise defined shall have the meanings
assigned to them in the Agreement.

     WHEREAS, the Corporation intends to issue and sell up to an additional
2,776,351 shares of Series E Convertible Preferred Stock, $.01 par value per
share, of the Corporation ("Series E Preferred Stock") to certain purchasers,
including certain Investors and new investors (the "New Investors") pursuant to
the Series E Convertible Preferred Stock Purchase Agreement dated May 22, 2001
by and between the Corporation and the Investors named on Schedule 1 attached
thereto, as amended on June 15, 2001 and August 1, 2003 (the "Purchase
Agreement"); and

     WHEREAS, the Corporation and the undersigned Investors desire to amend the
Agreement such that the New Investors shall be made a party thereto.

     NOW, THEREFORE, in consideration of the mutual covenants and agreements
contained herein, the receipt and sufficiency of which are hereby acknowledged,
the parties hereto agree as follows:

1.   AMENDMENTS TO THE AGREEMENT. Acting in accordance with Section 11 of the
Agreement, the Agreement is hereby amended as follows:

     (a)  SCHEDULE 1 of the Agreement is hereby amended and restated in its
entirety, as set forth on EXHIBIT A attached hereto, pursuant to which the New
Investors are added to Schedule 1 of the Agreement and each is thereby deemed an
"Investor" as such term is defined in the Agreement, subject to all of the
terms, conditions, benefits, rights, limitations and restrictions applicable to
Investors set forth therein.

     (b)  A new Section 20 shall be added to the Agreement which shall read as
follows:

          SECTION 20. ADDITIONAL SERIES E INVESTORS. Any person or entity that,
     on or after the date hereof, purchases Series E Preferred Shares pursuant
     to the Series E Stock Purchase Agreement and becomes an "Investor"
     thereunder may, with the prior written approval of the Corporation (but
     without the need for approval by any other party to this Agreement), become
     a party to this Agreement by executing and delivering a

<Page>

     counterpart signature page hereto, whereupon such person or entity shall be
     deemed an "Investor" and "Series E Investor" for all purposes of this
     Agreement.

2.   The Agreement, as supplemented and modified by this Amendment, together
with the other writings referred to in the Agreement or delivered pursuant
thereto which form a part thereof, contains the entire agreement among the
parties with respect to the subject matter thereof and amends, restates and
supersedes all prior and contemporaneous arrangements or understandings with
respect thereto.

4.   Upon the effectiveness of this Amendment, on and after the date hereof,
each reference in the Agreement to "this Agreement," "hereunder," "hereof,"
"herein" or words of like import, and each reference in the other documents
entered into in connection with the Agreement, shall mean and be a reference to
the Agreement, as amended hereby. Except as specifically amended above, the
Agreement shall remain in full force and effect and is hereby ratified and
confirmed.

5.   This Amendment shall be governed by, and construed and enforced in
accordance with, the substantive laws of the State of Delaware without regard to
its principles of conflicts of laws.

6.   This Amendment may be executed in any number of counterparts, and each such
counterpart shall be deemed to be an original instrument, but all such
counterparts together shall constitute but one agreement.

         [The remainder of this page has intentionally been left blank.]

                                      - 2 -
<Page>

     IN WITNESS WHEREOF, The Corporation and each of the parties set forth on
the foregoing signature pages have caused this Amendment No. 3 to Fourth Amended
and Restated Stockholders' Agreement to be executed as of the date first above
written.

                                      NITROMED, INC.

                                      By:   /s/ Joseph Grimm
                                         ---------------------------------------
                                           Name: Joseph Grimm
                                           Title: CFO

                                      HEALTHCARE VENTURES III, L.P.

                                      By:   HealthCare Partners III, L.P.,
                                            as General Partner

                                      By:   /s/ Jeffrey Steinberg
                                         ---------------------------------------
                                             Title: General Partner

                                      HEALTHCARE VENTURES IV, L. P.

                                      By:   HealthCare Partners IV, L. P.,
                                            as General Partner

                                      By:   s/s Jeffrey Steinberg
                                         ---------------------------------------
                                            Title: General Partner

                                      HEALTHCARE VENTURES V, L. P.

                                      By:   HealthCare Partners V, L. P.,
                                            as General Partner

                                      By:   /s/ Jeffrey Steinberg
                                         ---------------------------------------
                                           Title: General Partner

<Page>

                      [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                    HEALTHCARE VENTURES VI, L.P.

                                    By:   HealthCare Partners VI, L.P.,
                                          as General Partner

                                    By:  /s/ Jeffrey Steinberg
                                       -----------------------------------------
                                         Title:  General Partner

                                    RHO MANAGEMENT TRUST II

                                    By:   Rho Management Company, Inc.,
                                          as Investment Adviser

                                    By:   /s/ Joshua Ruch
                                       ----------------------------------------
                                          Title: CEO

                                    RHO VENTURES IV, L.P.

                                    By:   Rho Management Ventures IV, L.L.C.,
                                          as General Partner

                                    By:   /s/ Joshua Ruch
                                       -----------------------------------------
                                          Title: Managing Member

                                    RHO VENTURES IV GmbH & CO.
                                    BETEILIGUNGS KG

                                    By:   Rho Capital Partners Verwaltungs GmbH,
                                          as General Partner

                                    By:   /s/ Joshua Ruch
                                        ----------------------------------------
                                          Title: Managing Director

                                      - 4 -
<Page>

                      [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                      RHO VENTURES IV (QP), L.P.

                                      By:   Rho Management Ventures IV, L.L.C.,
                                            as General Partner

                                      By:  /s/ Joshua Ruch
                                          --------------------------------------
                                            Title: Managing Member

                                      ATLAS VENTURE FUND II, L.P.

                                      By:   Atlas Venture Associates II,
                                            L.P., as General Partner

                                      By:
                                          --------------------------------------
                                            Title: General Partner

                                      M & G EQUITIES, INC.

                                      By:
                                          --------------------------------------
                                            Title: President

                                      HUDSON TRUST

                                      By:
                                         ---------------------------------------
                                            Title:

                                      THE GOLDMAN SACHS GROUP, INC.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      - 5 -
<Page>

                      [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                      *THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      B.U.N.P.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      JOHNSON AND JOHNSON DEVELOPMENT
                                      CORPORATION

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      CURRAN PARTNERS L.P.

                                      By:
                                         ---------------------------------------
                                            Name:  John P. Curran
                                            Title: General Partner

                                      DELAWARE CHARTER AND TRUST
                                      JOHN P. CURRAN IRA

                                      By:
                                         ---------------------------------------
                                            Name:  John P. Curran
                                            Title: Self Directed IRA

----------
*     Except with respect to Sections 2.2, 2.4 through 2.14, 3.1 through 3.4,
3.6 and 5.1 through 5.5 of the Agreement, under which BWH has no rights,
liabilities or responsibilities.

                                      - 6 -
<Page>

                      [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                      SENTRON MEDICAL, INC.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      LOMBARD ODIER & CIE

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      BANK JULUIS BAER & CO. LTD.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      AETNA LIFE INSURANCE COMPANY

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      MYTHEN TREUHAND & VERWALTUNGS AG

                                      By:
                                         ---------------------------------------
                                            Title:

                                      BANK SARASIN & CO.

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      - 7 -
<Page>

                   [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                      GZB BANK (SCHWEIZ) AG

                                      By:
                                         ---------------------------------------
                                            Name:
                                            Title:

                                      ------------------------------------------
                                      Heinrich Hasler

                                      CC/M NITROMED HOLDINGS, L.P.

                                      By: /s/ David R. Ramsay
                                         ---------------------------------------
                                      Name:
                                      Title:

                                      CC NITROMED HOLDINGS, L.P.

                                      By: /s/ David R. Ramsay
                                         ---------------------------------------
                                      Name:
                                      Title:

                                      CC/Q PARTNERS, L.P.

                                      By: /s/ David R. Ramsay
                                         ---------------------------------------
                                      Name:
                                      Title:

                                      DC 1998 NFA TRUST

                                      By:
                                         ---------------------------------------
                                            Name:  Lee Casty
                                            Title: Trustee

                                      - 8 -
<Page>

                   [Signature Page to Amendment No. 3 to
              Fourth Amended and Restated Stockholder's Agreement]

                                            ------------------------------------
                                            James M. Casty

                                            ------------------------------------
                                            Lawrence Abrams

                                            ------------------------------------
                                            Robert Granovsky

                                            ------------------------------------
                                            **Manuel Worcel

                                            /s/ Michael D. Loberg
                                            ------------------------------------
                                            **Michael D. Loberg

                                            /s/ Joseph M. Grimm
                                            ------------------------------------
                                            **Joseph M. Grimm

                                            ------------------------------------
                                            **L. Gordon Letts

----------
**     Except with respect to Sections 2, 3.1 through 3.4, 3.6 and 5 hereof,
under which the signatory has no rights, liabilities or responsibilities.

                                      - 9 -
<Page>

                                                                       EXHIBIT A

                                   SCHEDULE 1

HealthCare Ventures III, L.P.
HealthCare Ventures IV, L.P.
HealthCare Ventures V, L.P.
HealthCare Ventures VI, L.P.
44 Nassau Street, Second Floor
Princeton, NJ 08543
Attn: Jeffrey Steinberg

Atlas Venture Fund II, L.P.
222 Berkeley Street
Boston, MA 02116
Attn: Jean-Francois Formela

Rho Management Trust II
Rho Ventures IV, L.P.
Rho Ventures IV GmbH & Co. Beteiligungs KG
Rho Ventures IV (QP), L.P.
c/o Rho Management Co., Inc.
152 W. 57th Street, 23rd Floor
New York, NY 10019
Attn: Chief Financial Officer

Hudson Trust
47 Hulfish Street
Princeton, NJ 08542
Attn: Thomas O'Dougherty

Lawrence Abrams
24 Central Park South
New York, NY 10019

M&G Equities, Inc.
c/o American Stock Transfer & Trust Co.
40 Wall Street
New York, NY 10005
Attn: Michael Karfunkel

The Brigham and
Women's Hospital, Inc.
75 Francis Street
Boston, MA 02115
Attn: Vandana D. Yajnick, Ph.D.

<Page>

Johnson & Johnson Development Corporation
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
Attn: Roger Guidi

Aetna Life Insurance Company
151 Farmington Avenue, RC21
Hartford, CT 06156-9000
Attn: David M. Clarke
       IG6U Private Equity Group

The Goldman Sachs Group, Inc.
85 Broad Street, 12th Floor
New York, NY 10004

B.U.N.P
c/o Boston University
Community Technology Fund
108 Bay State Road
Boston, MA 02215
Attn: Matthew Burns or Matthew Crowley

Curran Partners L.P.
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Delaware Charter and Trust
John P. Curran IRA
c/o Curran Capital Management
237 Park Avenue
New York, NY 10017
Attn: John P. Curran

Sentron Medical, Inc.
4445 Lake Forest Drive, Suite 600
Cincinnati, OH 45242
Attn: Dennis B. Costello
        Group Director, Venture Projects

Lombard Odier & Cie
Toedistr.36
8002 Zurich
Switzerland
Attn: Alexandre Meyer

                                     - 11 -
<Page>

Bank Julius Baer & Co. Ltd.
Bahnhofstr. 36
8001 Zurich
Switzerland
Attn: Claudio Studer

Mythen Treuhand & Verwaltungs AG
Splugenstrasse 9
8002 Zurich
Switzerland
Attn: Alex Fancelli

Robert Granovsky
c/o The Goldman Sachs Group
One New York Plaza
50th Floor
New York, NY 10004

Bank Sarasin & Co.
Elisabethenstrasse 62
CH-4002 Basel
Switzerland

GZB Bank (Schweiz) AG
Talacker 42
Zurich, Ch-8022
Switzerland

Heinrich Hasler
Nidelbadstr 90
Zurich, 8038
Switzerland

CC/M NitroMed Holdings, L.P.
CC NitroMed Holdings, L.P.
CC/Q Partners, L.P.
Care Capital Investments II, L.P.
c/o Care Capital LLC
Princeton Overlook One
100 Overlook Center & Route 1
Princeton, NJ 08540

DC 1998 NFA Trust
c/o IFX Corporation
Venture American Securities
707 Skokie Boulevard, Suite 580
Northbrook, IL 60062

                                     - 12 -
<Page>

James M. Casty
6185 Northwest Way
Boca Raton, FL 33496

Boston Scientific Corporation
One Boston Scientific Place
Natick, MA 01760-1537

                                     - 13 -<Page>

                                                                   Exhibit 10.17

                                 NitroMed, Inc.
                           Schedule of Warrantholders

<Table>
<Caption>
                                                                     EXERCISE
        ISSUED TO                     DATE        SHARES (1)          PRICE
      -------------                ----------     ----------         --------
<S>                                <C>                <C>                <C>
Aetna Life Insurance Co.           12/17/1997            163             0.08
Aetna Life Insurance Co.           12/17/1997            546             0.08
Aetna Life Insurance Co.           12/17/1997            274             0.08
Aetna Life Insurance Co.           12/17/1997            409             0.08
Aetna Life Insurance Co.           12/17/1997            409             0.08
Aetna Life Insurance Co.           12/17/1997            349             0.08
Aetna Life Insurance Co.           12/17/1997            291             0.08
Aetna Life Insurance Co.           12/17/1997            415             0.08
Aetna Life Insurance Co.           12/17/1997            582             0.08
Atlas Venture Fund II, L.P.         7/27/1994          7,811             0.08
Atlas Venture Fund II, L.P.         7/27/1994          2,343             0.08
Atlas Venture Fund II, L.P.         9/19/1994          3,905             0.08
Atlas Venture Fund II, L.P.        10/11/1994          5,859             0.08
Atlas Venture Fund II, L.P.        10/28/1994          5,859             0.08
Atlas Venture Fund II, L.P.        12/20/1994          8,332             0.08
Atlas Venture Fund II, L.P.         1/13/1995          4,999             0.08
Atlas Venture Fund II, L.P.         2/17/1995          4,166             0.08
Atlas Venture Fund II, L.P.         3/13/1995          5,940             0.08
Atlas Venture Fund II, L.P.         6/20/1995          7,812             0.08
Atlas Venture Fund II, L.P.         7/13/1995          3,906             0.08
Atlas Venture Fund II, L.P.         8/11/1995          3,906             0.08
Atlas Venture Fund II, L.P.         9/27/1995          3,906             0.08
Atlas Venture Fund II, L.P.        10/27/1995          3,906             0.08
Atlas Venture Fund II, L.P.         1/10/1996          7,542             0.08
Atlas Venture Fund II, L.P.          2/7/1996          7,543             0.08
Atlas Venture Fund II, L.P.         6/11/1996         15,388             0.08
Atlas Venture Fund II, L.P.         2/10/1997          6,250             0.08
Hudson Trust                        1/10/1996            225             0.08
Hudson Trust                         2/7/1996            221             0.08
Hudson Trust                        6/11/1996            318             0.08
Hudson Trust                        9/30/1996            111             0.08
Hudson Trust                       10/17/1996            111             0.08
Hudson Trust                       11/14/1996            111             0.08
Hudson Trust                       12/17/1996            111             0.08
Hudson Trust                        2/10/1997            111             0.08
M&G Equities, Inc.                  7/27/1994            158             0.08
M&G Equities, Inc.                  7/27/1994             47             0.08
M&G Equities, Inc.                  9/19/1994             72             0.08
M&G Equities, Inc.                 10/21/1994            119             0.08
M&G Equities, Inc.                 11/23/1994            119             0.08
M&G Equities, Inc.                  6/20/1995            520             0.08
M&G Equities, Inc.                  7/13/1995            260             0.08
M&G Equities, Inc.                  8/11/1995            260             0.08
M&G Equities, Inc.                  9/27/1995            260             0.08
M&G Equities, Inc.                 10/27/1995            260             0.08
M&G Equities, Inc.                  1/10/1996          2,582             0.08
M&G Equities, Inc.                   2/7/1996          2,560             0.08
M&G Equities, Inc.                  6/11/1996          4,140             0.08
M&G Equities, Inc.                  9/30/1996            150             0.08
M&G Equities, Inc.                 10/17/1996            150             0.08
M&G Equities, Inc.                 11/14/1996            150             0.08
M&G Equities, Inc.                  2/10/1997          1,250             0.08
Rho Management Trust II             8/22/2001          1,222             0.01
Rho Management Trust II             8/22/2001          1,222             0.01
Rho Management Trust II             8/22/2001          1,222             0.01
Rho Management Trust II             8/22/2001          1,222             0.01
</Table>

<Page>

                                 NitroMed, Inc.
                           Schedule of Warrantholders

<Table>
<Caption>
                                                                     EXERCISE
        ISSUED TO                     DATE        SHARES (1)          PRICE
      -------------                ----------     ----------         --------
<S>                                 <C>              <C>                 <C>
Rho Management Trust II             8/22/2001            569             0.01
Rho Management Trust II             8/22/2001          1,897             0.01
Rho Management Trust II             8/22/2001            953             0.01
Rho Management Trust II             8/22/2001          1,423             0.01
Rho Management Trust II             8/22/2001          1,423             0.01
Rho Management Trust II             8/22/2001            366             0.01
Rho Management Trust II             8/22/2001            305             0.01
Rho Management Trust II             8/22/2001            435             0.01
Rho Management Trust II             8/22/2001            611             0.01
Rho Management Trust II             8/22/2001          1,212             0.01
Rho Management Trust II             8/22/2001          1,734             0.01
Rho Management Trust II             8/22/2001            867             0.01
Rho Management Trust II             8/22/2001            867             0.01
Rho Management Trust II             8/22/2001            867             0.01
Rho Management Trust II             8/22/2001            867             0.01
Rho Management Trust II             8/22/2001          1,190             0.01
Rho Management Trust II             8/22/2001          1,222             0.01
Rho Management Trust II             8/22/2001          2,464             0.01
TOTAL:                                               151,347
</Table>

(1) Warrants issued prior to the Company's 8 for 1 reverse stock split on
    April 4, 1997 reflect post-split amounts.

<Page>

     THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE BEEN ACQUIRED FOR
INVESTMENT AND HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933. THESE
SECURITIES MAY NOT BE SOLD OR TRANSFERRED IN THE ABSENCE OF SUCH REGISTRATION OR
AN EXEMPTION THEREFROM UNDER SAID ACT.

           THIS WARRANT AND THE SHARES OF COMMON STOCK ISSUED UPON ITS
                   EXERCISE ARE SUBJECT TO THE RESTRICTIONS ON
                 TRANSFER SET FORTH IN SECTION 4 OF THIS WARRANT

Warrant No. __                                        Number of Shares: ________
                                                       (subject to adjustment)
Date of Issuance: ______

                                 NITROMED, INC.

                          COMMON STOCK PURCHASE WARRANT

                             (Void after __________)

     NitroMed, Inc., a Delaware corporation (the "Company"), for value received,
hereby certifies and agrees that ________________ or its registered assigns (the
"Registered Holder"), is entitled, subject to the terms set forth below, to
purchase from the Company, at any time or from time to time on or after the date
of issuance and on or before _________ at not later than 5:00 p.m. (Boston,
Massachusetts time), ______ shares of Common Stock, $.01 par value per share, of
the Company, at a purchase price of $.01 per share. The shares purchasable upon
exercise of this Warrant, and the purchase price per share, each as adjusted
from time to time pursuant to the provisions of this Warrant, are hereinafter
referred to as the "Warrant Shares" and the "Exercise Price," respectively. The
term "Warrant" as used herein shall include this Warrant and any other warrants
delivered in substitution or exchange therefor, as provided herein.

     1.   EXERCISE.

          (a)   This Warrant may be exercised by the Registered Holder, in whole
or in part, by surrendering this Warrant, with the Notice of Exercise form
appended hereto duly executed by such Registered Holder or by such Registered
Holder's duly authorized attorney, at the principal office of the Company, or at
such other office or agency as the Company may designate, accompanied by payment
in full, in lawful money of the United States, of the Exercise Price payable in
respect of the number of shares of Warrant Shares purchased upon such exercise.

          (b)   Each exercise of this Warrant shall be deemed to have been
effected immediately prior to the close of business on the day on which this
Warrant shall have been surrendered to the Company as provided in subsection
1(a) above. At such time, the person or persons in whose name or names any
certificates for Warrant Shares shall be issuable upon such exercise as provided
in subsection 1(c) below shall be deemed to have become the holder or holders of
record of the Warrant Shares represented by such certificates.

<Page>

          (c)   As soon as practicable after the exercise of this Warrant in
full or in part, and in any event within 10 days thereafter, the Company, at its
expense, will cause to be issued in the name of, and delivered to, the
Registered Holder, or as such Holder (upon payment by such Holder of any
applicable transfer taxes) may direct:

                (i)     a certificate or certificates for the number of full
Warrant Shares to which such Registered Holder shall be entitled upon such
exercise plus, in lieu of any fractional share to which such Registered Holder
would otherwise be entitled, cash in an amount determined pursuant to Section 3
hereof; and

                (ii)    in case such exercise is in part only, a new warrant or
warrants (dated the date hereof) of like tenor, calling in the aggregate on the
face or faces thereof for the number of Warrant Shares equal (without giving
effect to any adjustment therein) to the number of such shares called for on the
face of this Warrant minus the number of such shares purchased by the Registered
Holder upon such exercise as provided in subsection 1(a) above.

          (d)   Notwithstanding anything to the contrary contained in the first
paragraph of this Warrant, Section 1(a) or this Section 1(d), the Registered
Holder shall have the right to exercise this Warrant to receive shares of Common
Stock equal to the value (as determined below) of this Warrant by surrender of
this Warrant at the Company's office, together with the Notice of Exercise in
substantially the form attached hereto (the "Notice of Exercise"), without any
payment by wire transfer, cash, check or cancellation of indebtedness, in which
event the Company shall issue to the Registered Holder a number of shares of
Common Stock computed using the following formula:

              X    =      Y(A-B)
                          ------
                             A

Where:        X    =  The number of shares of Common Stock to be issued to the
                      Registered Holder.

              Y    =  The number of shares of Common Stock under this Warrant.

              A    =  The fair market value of one share of Common Stock.

              B    =  Exercise Price.

     As used herein, the fair market value of the Common Stock shall mean, with
respect to each share of Common Stock, the average of the closing prices of the
Company's Common Stock sold on all securities exchanges on which the Common
Stock may at the time be listed (including, for this purpose, the Nasdaq
National Market), or, if at any time the Common Stock is not so listed, the
average of the representative bid and asked prices quoted in the Nasdaq System
as of 4:00 p.m., New York City time, or, if at any time the Common Stock is not
quoted in the Nasdaq System, the average of the highest bid and lowest asked
price in the domestic over-the-counter market as reported by the National
Quotation Bureau, Incorporated, or any similar successor organization, in each
such case on the day on which the Notice of Exercise is

                                       -2-
<Page>

received or if no sales of the Common Stock have occurred on such date, on the
next preceding date on which there were such sales. If at any time the Common
Stock is not listed on any securities exchange or quoted in the Nasdaq System or
the over-the-counter market, the fair market value of the Common Stock shall be
the highest price per share which the Company could obtain from a willing buyer
(who is not a current employee or director) for shares of Common Stock sold by
the Company, from authorized but unissued shares, as determined in good faith by
the Board of Directors of the Company, unless (i) the Company shall become
subject to a merger, acquisition or other consolidation pursuant to which the
Company is not the surviving party, in which case the fair market value of the
Common Stock shall be deemed to be the value received by the holders of the
Company's Common Stock for each share of Common Stock pursuant to the Company's
acquisition; or (ii) the Registered Holder shall purchase such shares in
conjunction with the initial underwritten public offering of the Company's
Common Stock pursuant to a registration statement filed under the Securities Act
of 1933, in which case, the fair market value of the shares of Common Stock
subject to this Warrant shall be the price at which all registered shares of
Common Stock are sold to the public in such offering.

     2.   ADJUSTMENTS. The Exercise Price and the number of shares purchasable
hereunder are subject to adjustment from time to time as follows:

          (a)   STOCK DIVIDEND, SPLIT OR SUBDIVISION OF SHARES. If the number of
shares of Common Stock outstanding at any time after the date hereof is
increased or deemed increased by a stock dividend payable in shares of Common
Stock or other securities convertible into or exchangeable for shares of Common
Stock ("Equivalents") or by a subdivision or split-up of shares of Common Stock
or Equivalents (other than a change in par value, from par value to no par value
or from no par value to par value), then, following the effective date fixed for
the determination of holders of Common Stock or Equivalents entitled to receive
such stock dividend, subdivision or split-up, the Exercise Price shall be
appropriately decreased (but in no event shall the Exercise Price be decreased
below the par value of the Common Stock issuable upon exercise of this Warrant)
and the number of shares of Common Stock issuable on exercise of each Warrant
shall be increased in proportion to such increase in outstanding shares (on a
fully diluted basis).

          (b)   COMBINATION OF SHARES. If, at any time after the date hereof,
the number of shares of Common Stock outstanding is decreased by a combination
of the outstanding shares of Common Stock (other than a change in par value,
from par value to no par value or from no par value to par value), then,
following the effective date for such combination, the Exercise Price shall be
appropriately increased and the number of shares of Common Stock issuable on
exercise of each Warrant shall be decreased in proportion to such decrease in
outstanding shares.

          (c)   REORGANIZATIONS, CONSOLIDATIONS, ETC. In the event, at any time
after the date hereof, of any capital reorganization, or any reclassification of
the capital stock of the Company (other than a change in par value or from par
value to no par value or from no par value to par value or as a result of a
stock dividend or subdivision, split-up or combination of shares), or the
consolidation or merger of the Company with or into another person (other than
consolidation or merger in which the Company is the continuing corporation and
which does not result in any change in the powers, designations, preferences and
rights, or the qualifications,

                                       -3-
<Page>

limitations or restrictions, if any, of the capital stock of the Company as
amended from time to time) or of the sale or other disposition of all or
substantially all the properties and assets of the Company in its entirety to
any other person (any such transaction, an "Extraordinary Transaction"), then
this Warrant shall be exercisable for the kind and number of shares of stock or
other securities or property of the Company, or of the corporation resulting
from or surviving such Extraordinary Transaction, that a holder of the number of
shares of Common Stock deliverable (immediately prior to the effectiveness of
the Extraordinary Transaction) upon exercise of this Warrant would have been
entitled to receive upon such Extraordinary Transaction. The provisions of this
Section 2(c) shall similarly apply to successive Extraordinary Transactions.

          (d)   OTHER SITUATIONS. If a state of facts shall occur that, without
being specifically controlled by the provisions of this Section 2, would not
fairly protect the exercise rights of this Warrant in accordance with the
essential intent and principles of such provisions, then the Board of Directors
of the Company shall make an adjustment in the application of such provisions,
in accordance with such essential intent and principles, so as to protect such
exercise rights.

          (e)   SUBSEQUENT SALE OF STOCK. If the Company shall, at any time or
from time to time after the date of issuance of this Warrant, issue any shares
of Common Stock or other securities convertible into, or exchangeable or
exercisable for, shares of Common Stock, in each case other than Excluded Stock
(as defined in the Restated Certificate of Incorporation of the Company as
amended from time to time) for a consideration per share less than the
applicable Exercise Price in effect immediately prior to the issuance of such
Common Stock, or other securities, the Exercise Price in effect immediately
prior to each such issuance shall automatically (except as otherwise provided in
this Section 2(e)) be lowered to a price equal to the consideration per share
received by the Company upon such issuance. This Warrant shall thereafter be
exercisable for that number of shares of Common Stock which shall be computed by
multiplying the number of shares of Common Stock previously issuable under this
Warrant by the quotient of the Exercise Price in effect immediately prior to
such sale divided by the Exercise Price, as adjusted hereby. For the purposes of
any adjustment of the Exercise Price pursuant to this Section 2(e), the
calculation of the consideration received by the Company shall be as provided in
Section 2(h) below.

          (f)   CALCULATIONS. All calculations under this Section shall be made
to the nearest one-hundredth of a cent ($.0001) or to the nearest one-hundredth
of a share, as the case may be.

          (g)   CERTIFICATE AS TO ADJUSTMENTS. Upon the occurrence of each
adjustment or readjustment pursuant to this Section 2, the Company at its own
expense shall promptly compute such adjustment or readjustment in accordance
with the terms hereof and furnish to each Registered Holder a certificate
setting forth such adjustment or readjustment and showing in detail the facts
upon which such adjustment or readjustment is based. The Company shall, upon the
written request, at any time, of any such Holder, furnish or cause to be
furnished to such Holder a like certificate setting forth: (i) such adjustments
and readjustments; (ii) the Exercise

                                       -4-
<Page>

Price at the time in effect; and (iii) the number of shares and the amount, if
any, of other property that at the time would be received upon the exercise of
the Warrant.

          (h)   CALCULATING CONSIDERATION RECEIVED FOR NEW STOCK.

                (i)     In the case of the issuance of Common Stock in whole or
in part for cash, the consideration shall be deemed to be the amount of cash
paid therefor after deducting therefrom any discounts, commissions or other
expenses allowed, paid or incurred by the Company for any underwriting or
otherwise in connection with the issuance and sale thereof, plus the value of
any property other than cash received by the Company, determined as provided in
paragraph (ii) below.

                (ii)    In the case of the issuance of Common Stock for a
consideration in whole or in part in property other than cash, the value of the
such property or consideration other than cash shall be deemed to be the fair
market value of such property as determined in good faith by the Board of
Directors of the Company, irrespective of any accounting treatment.

                (iii)   In the case of the issuance of Common Stock for
consideration in whole or in part other than cash or property, the value of such
consideration shall be deemed to be the aggregate par value of such Common Stock
(or the aggregate stated value if such Common Stock has no par value), less the
value of any other consideration received by the Company, determined as provided
in paragraphs (i) and (ii) above.

                (iv)    In the case of the issuance of options or other rights
to purchase or subscribe for Common Stock, securities by their terms convertible
into or exchangeable for Common Stock or options to purchase or other rights to
subscribe for such convertible or exchangeable securities:

                        (A)   the aggregate maximum number of shares of Common
          Stock deliverable upon exercise of such options to purchase or rights
          to subscribe for Common Stock shall be deemed to have been issued at
          the time such options or rights were issued and for a consideration
          equal to the consideration (determined in the manner provided in
          paragraphs (i), (ii) and (iii) above), if any, received by the Company
          upon the issuance of such options or rights plus the minimum purchase
          price provided in such options or rights for the Common Stock covered
          thereby (the consideration in each case to be determined in the manner
          provided in paragraphs (i), (ii) and (iii) above);

                        (B)   the aggregate maximum number of shares of Common
          Stock deliverable upon conversion of, or in exchange for, any such
          convertible or exchangeable securities or upon the exercise of options
          to purchase or rights to subscribe for such convertible or
          exchangeable securities and subsequent conversion or exchange thereof
          shall be deemed to have been issued at the time such securities were
          issued or such options or rights were issued and for a consideration
          equal to the consideration received by the Company for any such
          securities and related options or rights (excluding any cash received
          on account of accrued interest or accrued dividends), plus the minimum
          additional

                                       -5-
<Page>

          consideration, if any, to be received by the Company upon the
          conversion or exchange of such securities or the exercise of any
          related options or rights (the consideration in each case to be
          determined in the manner provided in paragraphs (i), (ii) and (iii)
          above;

                        (C)   if there is any change in the exercise price of,
          or number of shares deliverable upon exercise of, any such options or
          rights or upon the conversion or exchange of any such convertible or
          exchangeable securities (other than a change resulting from the
          antidilution provisions thereof), then the Exercise Price shall
          automatically be readjusted in proportion to such change; and

                        (D)   upon the expiration of any such options or rights
          or the termination of any such rights to convert or exchange such
          convertible or exchangeable securities, the Exercise Price shall be
          automatically readjusted to the Exercise Price that would have
          obtained had such options, rights or convertible or exchangeable
          securities not been issued.

     3.   FRACTIONAL SHARES. The Company shall not be required upon the exercise
of this Warrant to issue any fractional shares, but shall make an adjustment
therefor in cash on the basis of the fair market value for each share of the
Company's Common Stock, determined in accordance with Section 1(d) hereof.

     4.   REQUIREMENTS FOR TRANSFER.

          (a)   WARRANT REGISTER. The Company will maintain a register (the
"Warrant Register") containing the names and addresses of the Registered Holder
or Registered Holders. Any Holder of this Warrant or any portion thereof may
change its address as shown on the Warrant Register by written notice to the
Company requesting such change, and the Company shall promptly make such change.
Until this Warrant is transferred on the Warrant Register of the Company, the
Company may treat the Holder as shown on the Warrant Register as the absolute
owner of this Warrant for all purposes, notwithstanding any notice to the
contrary, PROVIDED, HOWEVER, that if and when this Warrant is properly assigned
in blank, the Company may, but shall not be obligated to, treat the bearer
hereof as the absolute owner hereof for all purposes, notwithstanding any notice
to the contrary. This Warrant shall be transferable, including as to an Investor
as defined in the Stockholders' Agreement, dated as of December 3, 1993, by and
among the Company and the other signatories thereto, as amended (the
"Stockholders' Agreement"), among members of such Investor's Group (as defined
in Section 1 of the Stockholders' Agreement), subject to the provisions of
Section 3 of the Stockholders' Agreement; provided, however, that the notice
described in Section 3.3 of the Stockholders' Agreement may also be accompanied
by, and a Transfer (as defined in the Stockholders' Agreement) of this Warrant
may be effected in the event that the Registered Holder delivers to the Company
(unless waived by the Company), a representation letter of the Registered
Holder, in lieu of an opinion of counsel, reasonably satisfactory to the Company
setting forth facts which establish the basis to conclude that the sale or
transfer is exempt from the registration requirements of the Act (a
"Representation Letter"); and provided further that no such Representation
Letter shall be required in the event of a Transfer described in Sections 3.3(y)
and (z) of the Stockholders' Agreement.

                                       -6-
<Page>

          (b)   WARRANT AGENT. The Company may, by written notice to the
Registered Holder, appoint an agent (with its principal place of business in
Boston, Massachusetts or New York, New York) for the purpose of maintaining the
Warrant Register referred to in Section 4(a) above, issuing the Common Stock or
other securities then issuable upon the exercise of this Warrant, exchanging
this Warrant, replacing this Warrant or any or all of the foregoing. Thereafter,
any such registration, issuance, exchange, or replacement, as the case may be,
may be made at the office of such agent.

          (c)   RESTRICTIONS ON TRANSFER. The Registered Holder of this Warrant
by acceptance hereof agrees that the transfer of this Warrant and the Warrant
Shares are subject to the provisions of Section 3 of the Stockholders' Agreement
which include restrictions on transfer of the Warrant Shares solely for the
purpose of compliance with securities laws, and any transferee hereof shall, by
acceptance of this Warrant or the shares of Common Stock issued pursuant to this
Warrant, agree to by bound by Section 3 of the Stockholders' Agreement. Subject
to the provisions of Section 3 of the Stockholders' Agreement and this Section
4, this Warrant and all rights hereunder are transferable, in whole or in part,
upon the surrender of this Warrant with a properly executed assignment (in
substantially the form attached hereto) at the principal office of the Company.

          (d)   EXCHANGE OF WARRANT UPON A TRANSFER. On surrender of this
Warrant for exchange, properly endorsed on the Assignment attached hereto and
subject to the provisions of this Warrant and Section 3 of the Stockholders'
Agreement and with the limitations on assignments and transfers as contained in
this Section 4, the Company at its expense shall issue to or on the order of the
Registered Holder a new warrant or warrants of like tenor, in the name of the
Registered Holder or as the Holder (on payment by the Holder of any applicable
transfer taxes) may direct, for the number of shares issuable upon exercise
hereof.

     5.   NO IMPAIRMENT. The Company will not, by amendment of its charter or
through reorganization, consolidation, merger, dissolution, sale of assets or
any other voluntary action, avoid or seek to avoid the observance or performance
of any of the terms of this Warrant, but will at all times carry out all such
terms and take all such action as may be reasonably necessary or appropriate in
order to protect the rights of the holder of this Warrant against impairment.

     6.   LIQUIDATING DIVIDENDS. If the Company pays a dividend or makes a
distribution on the Common Stock payable otherwise than in cash out of earnings
or earned surplus (determined in accordance with generally accepted accounting
principles) except for a stock dividend payable in shares of Common Stock (a
"Liquidating Dividend"), then the Company will pay or distribute to the
Registered Holder of this Warrant, upon the exercise hereof, in addition to the
Warrant Shares purchased upon such exercise, the Liquidating Dividend which
would have been paid to such Registered Holder if he had been the owner of
record of such Warrant Shares immediately prior to the date on which a record is
taken for such Liquidating Dividend or, if no record is taken, the date as of
which the record holders of Common Stock entitled to such dividends or
distribution are to be determined.

                                       -7-
<Page>

     7.   NOTICES OF RECORD DATE, ETC. In case:

          (a)   the Company shall take a record of the holders of its Common
Stock (or other stock or securities at the time deliverable upon the exercise of
this Warrant) for the purpose of entitling or enabling them to receive any
dividend or other distribution, or to receive any right to subscribe for or
purchase any shares of stock of any class or any other securities, or to receive
any other right; or

          (b)   of any capital reorganization of the Company, any
reclassification of the capital stock of the Company, any consolidation or
merger of the Company with or into another corporation (other than a
consolidation or merger in which the Company is the surviving entity), or any
transfer of all or substantially all of the assets of the Company; or

          (c)   of the voluntary or involuntary dissolution, liquidation or
winding-up of the Company, then, and in each such case, the Company will mail or
cause to be mailed to the Registered Holder of this Warrant a notice specifying,
as the case may be, (i) the date on which a record is to be taken for the
purpose of such dividend, distribution or right, and stating the amount and
character of such dividend, distribution or right, or (ii) the effective date on
which such reorganization, reclassification, consolidation, merger, transfer,
dissolution, liquidation or winding-up is to take place, and the time, if any is
to be fixed, as of which the holders of record of Common Stock (or such other
stock or securities at the time deliverable upon the exercise of this Warrant)
shall be entitled to exchange their shares of Common Stock (or such other stock
or securities) for securities or other property deliverable upon such
reorganization, reclassification, consolidation, merger, transfer, dissolution,
liquidation or winding-up. Such notice shall be mailed at least twenty (20) days
prior to the record date or effective date for the event specified in such
notice.

     8.   RESERVATION OF STOCK. The Company will at all times reserve and keep
available, solely for issuance and delivery upon the exercise of this Warrant,
such number of Warrant Shares and other stock, securities and property, as from
time to time shall be issuable upon the exercise of this Warrant.

     9.   REPLACEMENT OF WARRANTS. Upon receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of
this Warrant and (in the case of loss, theft or destruction) upon delivery of an
indemnity agreement reasonably satisfactory to the Company, or (in the case of
mutilation) upon surrender and cancellation of this Warrant, the Company will
issue, in lieu thereof, a new Warrant of like tenor.

     10.  MAILING OF NOTICES, ETC. All notices and other communications from the
Company to the Registered Holder of this Warrant shall be mailed by first-class
certified or registered mail, postage prepaid, to the address furnished to the
Company in writing by the last Registered Holder of this Warrant who shall have
furnished an address to the Company in writing. All notices and other
communications from the Registered Holder of this Warrant or in connection
herewith to the Company shall be mailed by first-class certified or registered
mail, postage prepaid, to the Company at its principal office set forth below.
If the Company should at any time change the location of its principal office to
a place other than as set forth below, it shall give prompt written notice to
the Registered Holder of this Warrant and thereafter all references

                                      -8-
<Page>

in this Warrant to the location of its principal office at the particular time
shall be as so specified in such notice.

     11.  NO RIGHTS AS STOCKHOLDER. Until the exercise of this Warrant, the
Registered Holder of this Warrant shall not have or exercise any rights by
virtue hereof as a stockholder of the Company.

     12.  CHANGE OR WAIVER. Any term of this Warrant may be changed or waived
only by an instrument in writing signed by the party against which enforcement
of the change or waiver is sought.

     13.  HEADINGS. The headings in this Warrant are for purposes of reference
only and shall not limit or otherwise affect the meaning of any provision of
this Warrant.

     14.  GOVERNING LAW. This Warrant will be governed by and construed in
accordance with the laws of the Commonwealth of Massachusetts.

     15.  CERTIFICATE. Upon request by the Registered Holder of this Warrant,
the Company shall promptly deliver to such holder a certificate executed by its
President or Chief Financial officer setting forth the total number of
outstanding shares of capital stock, convertible debt instruments and options,
rights, warrants or other agreements relating to the purchase of such capital
stock or convertible debt instruments, together with its calculation of the
number of shares remaining available for issuance upon exercise of this Warrant,
and a certificate of the accuracy of the statements set forth therein.

     16.  INJUNCTIVE RELIEF. The parties agree that any breach of this Warrant
by the Company is likely to cause the Registered Holder irreparable damage and,
therefore, in the event of any such breach, the Company agrees that the
Registered Holder shall be entitled, in addition to such other remedies which
may be available, to specific performance and other injunctive relief.

                                 NITROMED, INC.

                                 By:
                                        ------------------------------------
                                        President and Chief Executive Officer

[Corporate Seal]
ATTEST:

--------------------
Secretary

                                       -9-
<Page>

                             NOTICE OF EXERCISE FORM

To:                                            Dated:
   -------------------------------                   ---------------------------

     The undersigned, pursuant to the provisions set forth in the attached
Warrant (No. __), hereby irrevocably elects to purchase ________ shares of the
Common Stock covered by such Warrant and herewith makes payment of $__________,
representing the full purchase price for such shares at the price per share
provided for in such Warrant.

                                            Signature:
                                                      --------------------------

                                            Address:
                                                      --------------------------

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

                                      -10-
<Page>

                                 ASSIGNMENT FORM

     FOR VALUE RECEIVED, hereby sells, assigns and transfers all of the rights
of the undersigned under the attached Warrant (No. __) with respect to the
number of shares of Common Stock covered thereby set forth below, unto:

<Table>
<Caption>
Name of Assignee                 Address                        No. of Shares
----------------                 -------                        -------------
<S>                              <C>                            <C>

</Table>

Dated:                           Signature:
      -----------------------              -------------------------------------

Dated:                           Witness:
      -----------------------              -------------------------------------

                                      -11-

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