Document:

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                                                                   Exhibit 10.17

                            COMBINATORX, INCORPORATED

                           SECOND AMENDED AND RESTATED
                           INVESTORS' RIGHTS AGREEMENT

                          DATED AS OF FEBRUARY 18, 2004

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<S>                                                                                                              <C>
1.   REGISTRATION RIGHTS..........................................................................................1

   1.1   DEFINITIONS..............................................................................................1
   1.2   REQUEST FOR REGISTRATION.................................................................................3
   1.3   COMPANY REGISTRATION.....................................................................................4
   1.4   OBLIGATIONS OF THE COMPANY...............................................................................5
   1.5   FURNISH INFORMATION......................................................................................6
   1.6   EXPENSES OF REGISTRATION.................................................................................7
   1.7   UNDERWRITING REQUIREMENTS................................................................................7
   1.8   DELAY OF REGISTRATION....................................................................................7
   1.9   INDEMNIFICATION..........................................................................................8
   1.10  REPORTS UNDER SECURITIES EXCHANGE ACT OF 1934...........................................................10
   1.11  FORM S-3 REGISTRATION...................................................................................11
   1.12  MARKET STAND-OFF AGREEMENT..............................................................................12
   1.13  TERMINATION OF REGISTRATION RIGHTS......................................................................12
   1.14  FUTURE ISSUANCES OF SECURITIES..........................................................................12

2.   COVENANTS...................................................................................................13

   2.1   DELIVERY OF FINANCIAL STATEMENTS........................................................................13
   2.2   RIGHT OF FIRST OFFER....................................................................................13
   2.3   INSPECTION..............................................................................................16
   2.4   TERMINATION OF CERTAIN COVENANTS........................................................................16

3.   COVENANTS...................................................................................................16

   3.1   NEGATIVE COVENANTS......................................................................................16
   3.2   AFFIRMATIVE COVENANTS...................................................................................17
   3.3   TERMINATION.............................................................................................18

4.   DIRECTED SHARE PROGRAM......................................................................................18

5.   MISCELLANEOUS...............................................................................................19

   5.1   SUCCESSORS..............................................................................................19
   5.2   GOVERNING LAW...........................................................................................20
   5.3   COUNTERPARTS............................................................................................20
   5.4   TITLES AND SUBTITLES....................................................................................20
   5.5   NOTICES.................................................................................................20
   5.6   ATTORNEY'S FEES.........................................................................................20
   5.7   AMENDMENTS OR WAIVER....................................................................................21
   5.8   SEVERABILITY............................................................................................21
   5.9   AGGREGATION OF STOCK....................................................................................21
   5.10  ENTIRE AGREEMENT........................................................................................21
   5.11  SPECIFIC PERFORMANCE....................................................................................21
   5.12  WAIVER..................................................................................................21
</Table>

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                            COMBINATORX, INCORPORATED

                           SECOND AMENDED AND RESTATED
                           INVESTORS' RIGHTS AGREEMENT

     This Second Amended and Restated Investors' Rights Agreement (the
"Agreement") is made and entered into as of this 18th day of February, 2004 by
and among CombinatoRx, Incorporated, a Delaware corporation (the "Company") and
the persons and entities listed on Schedule A attached hereto (the "Investors").

                                    RECITALS

     WHEREAS, the parties desire to enter into this Agreement in connection with
the issuance and sale of shares of the Company's Series D Preferred Stock,
$0.001 par value per share (the "Series D Preferred Stock") to certain of the
Investors (the "Transaction").

     WHEREAS, the Investors desire to be granted the rights created herein.

     WHEREAS, the parties desire to amend and restate the First Amended and
Restated Investors' Rights Agreement (the "First Amended Investors' Rights
Agreement") dated September 10, 2002 by and among the Company and the Investors
(as such term is defined in the First Amended Investors' Rights Agreement).

     NOW, THEREFORE, in consideration of the premises and for other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:

                                    AGREEMENT

     1.   REGISTRATION RIGHTS.  The Company covenants and agrees as follows:

          1.1     DEFINITIONS.  For purposes of this Agreement:

                  (a)    The term "1934 Act" shall mean the Securities Exchange
Act of 1934, as amended, or any successor federal statute, and the rules and
regulations of the SEC issued under such act, as they each may, from time to
time be in effect.

                  (b)    The term "Act" means the Securities Act of 1933, as
amended, or any successor federal statute, and the rules and regulations of the
SEC issued under such act, as they each may, from time to time, be in effect.

                  (c)    The term "Basic Amount" means, with respect to a
Qualified Investor, its pro rata portion of the Offered Securities determined by
multiplying the number of Offered Securities by a fraction, the numerator of
which is the aggregate number of shares of Common Stock then held by such
Qualified Investor (giving effect to the conversion into Common Stock of all
shares of convertible preferred stock then held by such Qualified Investor) and
the denominator of which is the total number of shares of Common Stock then held
by all of

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the Qualified Investors (giving effect to the conversion into Common Stock of
all outstanding shares of convertible preferred stock).

                  (d)    The term "Common Stock" means the Company's common
stock, $0.001 par value per share.

                  (e)    The term "Form S-3" means such form under the Act as in
effect on the date hereof or any registration statement under the Act
subsequently adopted by the SEC which permits inclusion or incorporation of
substantial information by reference to other documents filed by the Company
with the SEC.

                  (f)    The term "Holder" means any person owning Registrable
Securities or any assignee thereof.

                  (g)    The term "Offered Securities" means (i) any shares of
its Common Stock, (ii) any other equity securities of the Company, including,
without limitation, shares of preferred stock, (iii) any option, warrant or
other right to subscribe for, purchase or otherwise acquire any equity
securities of the Company, or (iv) any debt securities convertible into capital
stock of the Company.

                  (h)    The term "Qualified Investor" means an Investor that is
an "accredited investor" within the meaning of Rule 501 promulgated under the
Act.

                  (i)    The term "register," "registered," and "registration"
refer to a registration of the capital stock of the Company effected by filing a
registration statement or similar document in compliance with the Act, and the
declaration or ordering of effectiveness of such registration statement or
document by the SEC pursuant to which such capital stock of the Company may be
sold to the public.

                  (j)    The term "Registrable Securities" means (i) the Common
Stock issuable or issued upon conversion of the Series Preferred Stock, (ii) any
Common Stock acquired by an Investor pursuant to Section 2.2 hereof or any other
preemptive right or right of first refusal granted to an Investor (including,
but not limited to, any Common Stock acquired pursuant to the Second Amended and
Restated Co-Sale Agreement by and among the Company, Preferred Stockholders,
Founders and Management Members); and (iii) any Common Stock of the Company
issued as, or in connection with (or issuable upon the conversion or exercise of
any warrant, right or other security which is issued as, or in connection with),
a stock dividend, stock split, recapitalization, reclassification or other
similar event with respect to, or in exchange for or in replacement of the
shares referenced in (i) and (ii) above.

                  (k)    The number of shares of "Registrable Securities then
outstanding" shall be determined by the number of shares of Common Stock
outstanding which are Registrable Securities and the number of shares of Common
Stock issuable pursuant to then exercisable or convertible securities which are
Registrable Securities.

                  (l)    The term "SEC" shall mean the Securities and Exchange
Commission or any other federal agency at the time administering the Act.

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                  (m)    The term "Series Preferred Stock" shall mean the
Series A Preferred Stock of the Company, $0.001 par value per share, the Series
B Preferred Stock of the Company, $0.001 par value per share, the Series C
Preferred Stock, $0.001 par value per share and the Series D Preferred Stock.

          1.2     REQUEST FOR REGISTRATION.

                  (a)    If the Company shall receive, at any time after six (6)
months after the effective date of the first registration statement filed by the
Company for an underwritten public offering of securities of the Company, a
written request from the Holders of at least twenty-five percent (25%) of the
Registrable Securities then outstanding that the Company file a registration
statement on Form S-1 or Form S-2 (or any successor form) under the Act covering
the registration of all or any portion of the Registrable Securities then
outstanding having an aggregate value of at least $5,000,000, then the Company
shall:

                         (i)     within ten (10) days of the receipt thereof,
give written notice of such request to all Holders in accordance with Section
5.5 and such Holders shall have the right, by giving written notice to the
Company within twenty (20) days after the Company provides its notice, to elect
to have included in such registration such of their Registrable Securities as
such Holder may request in such notice of election; and

                         (ii)    use best efforts to effect, as soon as
practicable after receipt of such request, to file such registration under the
Act on Form S-1 or Form S-2 (or any successor form) of all Registrable
Securities which the Holders request to be registered, subject to the
limitations of subsection 1.2(b), within 30 days of the mailing of such notice
by the Company to Holders pursuant to Section 1.2(a)(i) hereof (but in no event
shall such filing be made prior to the 20 day period the Holders have to elect
to register Registrable Shares).

                  (b)    If the Holders initiating the registration request
hereunder ("Initiating Holders") intend to distribute the Registrable Securities
covered by their request by means of an underwriting, they shall so advise the
Company as a part of their request made pursuant to subsection 1.2(a) and the
Company shall include such information in the written notice referred to in
subsection 1.2(a)(i). The underwriter will be selected by the Initiating Holders
and shall be subject to the approval of the Company, which approval will not be
unreasonably withheld, conditioned or delayed. All Holders proposing to
distribute their securities through such underwriting shall (together with the
Company as provided in subsection 1.4(e)) enter into an underwriting agreement
in customary form with the underwriter or underwriters selected for such
underwriting; provided that such underwriting agreement shall not provide for
indemnification or contribution obligations on the part of the Holders
materially greater than the obligations of the Holders pursuant to Section 1.9
of this Agreement. In such event, the right of any Holder to include his
Registrable Securities in such registration shall be conditioned upon such
Holder's participation in such underwriting and the inclusion of such Holder's
Registrable Securities in the underwriting (unless otherwise mutually agreed by
a majority in interest of the Initiating Holders and such Holder) to the extent
provided herein. If any Holder who has requested inclusion of its Registrable
Shares in such registration as provided herein disapproves of the terms of the
underwriting, such Holder may elect, by written notice to the Company, to
withdraw its Registrable Shares from such registration statement and

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underwriting. Notwithstanding any other provision of this Section 1.2(b), if the
underwriter advises the Initiating Holders in writing that marketing factors
require a limitation of the number of shares to be underwritten, then the
Initiating Holders shall so advise all Holders of Registrable Securities which
would otherwise be underwritten pursuant hereto, and the number of shares of
Registrable Securities that may be included in the underwriting shall be
allocated among all Holders thereof, including the Initiating Holders, in
proportion (as nearly as practicable) to the amount of Registrable Securities of
the Company owned by each Holder; PROVIDED, HOWEVER, that the number of shares
of Registrable Securities to be included in such underwriting shall not be
reduced unless all other securities held by any stockholder other than a Holder
are first entirely excluded from the underwriting.

                  (c)    Notwithstanding the foregoing, if the Company shall
furnish to Holders requesting a registration statement pursuant to this Section
1.2, a certificate signed by the Chief Executive Officer of the Company stating
that, in the good faith judgment of the Board of Directors of the Company, it
would be seriously detrimental to the Company and its stockholders for such
registration statement to be filed and it is therefore essential to defer the
filing of such registration statement, the Company shall have the right to defer
taking action with respect to such filing for a period of not more than 35 days
after receipt of the request of the Initiating Holders under Section 1.2 of this
Agreement; PROVIDED, HOWEVER, that the Company may not utilize this right more
than once in any twelve-month period.

                  (d)    In addition, the Company shall not be obligated to
effect, or to take any action to effect, any registration pursuant to this
Section 1.2:

                         (i)     After the Company has effected two (2)
registrations pursuant to this Section 1.2 and such registrations have been
declared or ordered effective, provided, however that a registration statement
shall not be counted if, as a result of the underwriter's cut-back, less than
50% of the total Registrable Shares that Holders have requested to be included
in the registration statement are so included; or

                         (ii)    During the period starting with the date seven
(7) days prior to the Company's good faith estimate of the date of filing of,
and ending on a date forty-five (45) days after the effective date of, a
registration subject to Section 1.3 hereof, provided that the Company is
actively employing in good faith all reasonable efforts to cause such
registration statement to become effective.

          1.3     COMPANY REGISTRATION. If at any time and from time to time
after the effective date of the first registration statement for a public
offering of securities of the Company, the Company proposes to register
(including for this purpose a registration effected by the Company for
stockholders other than the Holders) any of its stock or other securities under
the Act in connection with the public offering of such securities, the Company
shall, at such time, promptly give each Holder written notice of such
registration and the intended method for distributing such stock or securities
in accordance with Section 5.5. Upon the written request of each Holder mailed
to the Company within twenty (20) days after the mailing of such notice by the
Company, the Company shall, subject to the provisions of Section 1.7, cause to
be registered, in the proposed registration statement referenced in the
Company's notice to the Holders pursuant to this Section 1.3, under the Act all
of the Registrable Securities that each such Holder

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has requested to be registered such that such Registrable Securities may be
distributed in accordance with the intended method of distribution specified in
the Company's notice to the Holders.

          1.4     OBLIGATIONS OF THE COMPANY. Whenever required under this
Section 1 to effect the registration of any Registrable Securities, the Company
shall, as expeditiously as possible:

                  (a)    Prepare and file with the SEC a registration statement
with respect to such Registrable Securities and use its best efforts to cause
such registration statement to become effective as soon as possible and, upon
the request of the Holders of a majority of the Registrable Securities
registered thereunder, keep such registration statement effective for a period
of up to six (6) months or until the distribution contemplated in the
Registration Statement has been completed; PROVIDED, HOWEVER, that (i) such six
(6) month period shall be extended for a period of time equal to the period the
Holder refrains from selling any securities included in such registration at the
request of an underwriter of Common Stock (or other securities) of the Company;
and (ii) in the case of any registration of Registrable Securities on Form S-3
which are intended to be offered on a continuous or delayed basis, such six (6)
month period shall be extended, if necessary, to keep the registration statement
effective until all such Registrable Securities are sold, provided that Rule
415, or any successor rule under the Act, permits an offering on a continuous or
delayed basis, and provided further that applicable rules under the Act
governing the obligation to file a post-effective amendment permit, in lieu of
filing a post-effective amendment which (I) includes any prospectus required by
Section 10(a)(3) of the Act or (II) reflects facts or events representing a
material or fundamental change in the information set forth in the registration
statement, the incorporation by reference of information required to be included
in (I) and (II) above to be contained in periodic reports filed pursuant to
Section 13 or 15(d) of the 1934 Act in the registration statement.

                  (b)    Prepare and file with the SEC such amendments and
supplements to such registration statement and the prospectus used in connection
with such registration statement as may be necessary to comply with the
provisions of the Act with respect to the disposition of all securities covered
by such registration statement.

                  (c)    Furnish to the Holders such numbers of copies of a
prospectus, including a preliminary prospectus, in conformity with the
requirements of the Act, and such other documents as any Holder may reasonably
request in order to facilitate the disposition of Registrable Securities owned
by such Holder.

                  (d)    Use its best efforts to register and qualify the
Registrable Securities covered by such registration statement under such other
securities or Blue Sky laws of such jurisdictions as shall be reasonably
requested by the Holders and do any and all other acts and things that may be
necessary or desirable to enable the Holder to consummate the public sale or
other disposition in such states of the Registrable Securities owned by the
Holders; PROVIDED that the Company shall not be required in connection therewith
or as a condition thereto to qualify to do business or to file a general consent
to service of process in any such states or jurisdictions, unless the Company is
already subject to service in such jurisdiction and except as may be required by
the Act.

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                  (e)    In the event of any underwritten public offering, enter
into and perform its obligations under an underwriting agreement, in usual and
customary form, with the managing underwriter of such offering. Each Holder
participating in such underwriting shall also enter into and perform its
obligations under such an agreement subject to the terms and conditions set
forth in Section 1.2(b) of this Agreement.

                  (f)    Notify each Holder of Registrable Securities covered by
such registration statement at any time when a prospectus relating thereto is
required to be delivered under the Act of the happening of any event as a result
of which the prospectus included in such registration statement, as then in
effect, includes an untrue statement of a material fact or omits to state a
material fact required to be stated therein or necessary to make the statements
therein not misleading in the light of the circumstances then existing.

                  (g)    Cause all such Registrable Securities to be listed on
each securities exchange or automated quotation system on which similar
securities issued by the Company are then listed.

                  (h)    Provide a transfer agent and registrar for all
Registrable Securities registered hereunder and a CUSIP number for all such
Registrable Securities, in each case not later than the effective date of such
registration.

                  (i)    Obtain a "cold comfort" letter from the Company's
independent public accountants in customary form and covering such matters of
the type customarily covered by "cold comfort" letters and obtain a customary
opinion of legal counsel for the Company, each as the holders of a majority of
the Registrable Securities being sold reasonably request.

                  (j)    Make available for inspection by the Holders, any
managing underwriter participating in any disposition pursuant to such
registration statement, and any attorney or accountant or other agent retained
by any such underwriter or selected by the Holders, all financial and other
records, pertinent corporate documents and properties of the Company and cause
the Company's officers, directors, employees and independent accounts to supply
all information reasonably requested by any such Holder, underwriter, attorney,
accountant or agent in connection with such registration statement;

                  (k)    Notify each Holder, promptly after it shall receive
notice thereof, of the time when such registration statement has become
effective or a supplement to any prospectus forming a part of such registration
statement has been filed; and

                  (l)    Following the effectiveness of a registration
statement, notify each seller of such Registrable Shares of any request by the
SEC for the amending or supplementing of such registration statement or
prospectus.

          1.5     FURNISH INFORMATION. It shall be a condition precedent to the
obligations of the Company to take any action pursuant to this Section 1 with
respect to the Registrable Securities of any selling Holder that such Holder
shall furnish to the Company such information regarding itself, the Registrable
Securities held by it, and the intended method of disposition of such securities
as shall be required to effect the registration of such Holder's Registrable
Securities.

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          1.6     EXPENSES OF REGISTRATION. The Company shall bear and pay all
expenses, other than underwriting discounts and commissions relating to the
disposition or sale of the Registrable Securities, incurred in connection with
any registration, filing or qualification of Registrable Securities with respect
to the registrations to be effected by the Company pursuant to this Agreement
for each Holder, including, without limitation, all registration, filing and
qualification fees, printers' and accounting fees relating and the reasonable
fees and disbursements of one counsel for the selling Holders selected by such
selling Holders; PROVIDED, HOWEVER, that the Company shall not be required to
pay for any expenses of any registration proceeding begun pursuant to this
Agreement if the registration request is subsequently withdrawn at the request
of the Holders of a majority of the Registrable Securities (other than as a
result of information concerning the business or financial condition of the
Company which is made known to the Holders after the date on which such
registration was requested) to be registered pursuant to such request (in which
case all participating Holders shall bear such expenses), unless the Holders of
a majority of the Registrable Securities agree to forfeit their right to one of
the two demand registrations pursuant to Section 1.2.

          1.7     UNDERWRITING REQUIREMENTS. In connection with any offering
involving an underwriting of shares of the Company's capital stock, the Company
shall not be required under Section 1.3 to include any of the Holders'
securities in such underwriting unless such Holders accept the terms of the
underwriting as agreed upon between the Company and the underwriters selected by
the Company; provided that such underwriting agreement shall not provide for
indemnification or contribution obligations on the part of the Holders
materially greater than the obligations of the Holders pursuant to Section 1.9
of this Agreement. If any Holder who has requested inclusion of its Registrable
Shares in such registration as provided herein disapproves of the terms of the
underwriting, such Holder may elect, by written notice to the Company, to
withdraw its Registrable Shares from such registration statement and
underwriting. If the managing underwriter advises the Company in writing that
marketing factors require a limitation on the number of shares to be
underwritten in connection with such registration, the securities of the Company
held by stock holders other than the Holders and offered by the Company shall be
excluded from such registration statement and underwriting to the extent deemed
advisable by the managing underwriter, and, if a further reduction of the number
of shares to be registered thereunder is required, the number of shares that may
be included in such registration statement and underwriting shall be allocated
among all Holders requesting registration in proportion, as nearly as
practicable, to the respective number of shares of Common Stock (on an
as-converted basis) held by them on the date the Company gives the notice
specified in Section 1.3; PROVIDED that, unless such registration is in
connection with the Company's initial public offering, the number of Registrable
Securities permitted to be included therein shall in any event be at least fifty
percent (50%) of the securities included therein (based on aggregate market
values). If any Holder would thus be entitled to include more shares than such
holder requested to be registered, the excess shall be allocated among other
requesting Holders pro rata in the manner described in the preceding sentence.

          1.8     DELAY OF REGISTRATION. No Holder shall have any right to
obtain or seek an injunction restraining or otherwise delaying any such
registration as the result of any controversy that might arise with respect to
the interpretation or implementation of this Section l.

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          1.9     INDEMNIFICATION.  In the event any Registrable Securities are
included in any registration statement under this Section 1:

                  (a)    The Company will indemnify and hold harmless each
Holder (and any partner, member or officer of such Holder), any underwriter (as
defined in the Act) for such Holder and each person, if any, who controls such
Holder or underwriter within the meaning of the Act or the 1934 Act, against any
expenses, losses, claims, damages, or liabilities (joint or several) to which
such Holder, underwriter or controlling person may become subject under the Act,
the 1934 Act or other federal or state law, insofar as such expenses, losses,
claims, damages, or liabilities (or actions in respect thereof) arise out of or
are based upon any of the following statements, omissions or violations
(collectively, a "Violation"): (i) any untrue statement or alleged untrue
statement of a material fact contained in such registration statement under
which such Registrable Shares were registered under the Act, including any
preliminary prospectus or final prospectus contained therein or any amendments
or supplements thereto, (ii) 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 (iii) any violation or alleged violation by the
Company of the Act, the 1934 Act, any state securities law or any rule or
regulation promulgated under the Act, the 1934 Act or any state securities law
or any other federal, state or common law in connection with the registration
statement or the offering contemplated thereby; and the Company will pay to each
such Holder, underwriter or controlling person of such Holder or underwriter any
legal or other expenses reasonably incurred by such Holder, underwriter or
controlling person in connection with investigating or defending any such
expense, loss, claim, damage, liability, or action; PROVIDED, HOWEVER, that the
indemnification provided in this subsection 1.9(a) shall not apply to amounts
paid in settlement of any such loss, claim, damage, liability, or action if such
settlement is effected without the consent of the Company (which consent shall
not be unreasonably withheld, conditioned or delayed), nor shall the Company be
liable for any expense, loss, claim, damage, liability, or action to the extent
that it arises out of or is based upon a Violation which occurs in reliance upon
and in conformity with written information furnished by the Holder to the
Company expressly for use in connection with such registration of such Holder's
Registrable Shares by such Holder, underwriter or controlling person.

                  (b)    Each Holder selling its Registrable Shares, severally,
and not jointly, will indemnify and hold harmless the Company, each of its
directors, each of its officers who has signed the registration statement, each
person, if any, who controls the Company within the meaning of the Act, any
underwriter, any other Holder selling securities in such registration statement
and any controlling person of any such underwriter or other Holder, against any
expenses, losses, claims, damages, or liabilities to which any of the foregoing
persons may become subject, under the Act, the 1934 Act or other federal or
state law, insofar as such expenses, losses, claims, damages, or liabilities (or
actions in respect thereto) arise out of or are based upon any (i) untrue
statement or alleged untrue statement of a material fact contained in such
registration statement, including any preliminary prospectus or final prospectus
contained therein or any amendments or supplements thereto, or (ii) 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,
(collectively, the "Holder Violation"), in each case to the extent (and only to
the extent) that such Holder Violation occurs in reliance upon and in conformity
with written information furnished by such Holder to the Company expressly for
use in connection

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with such registration; and each such Holder will pay any legal or other
expenses reasonably incurred by any person intended to be indemnified pursuant
to this subsection 1.9(b), in connection with investigating or defending any
such expense, loss, claim, damage, liability, or action; PROVIDED, HOWEVER, that
the indemnity agreement contained in this subsection 1.9(b) shall not apply to
amounts paid in settlement of any such expense, loss, claim, damage, liability
or action if such settlement is effected without the consent of the Holder,
which consent shall not be unreasonably withheld; PROVIDED that, in no event
shall any indemnity under this subsection 1.9(b) exceed the net proceeds to such
Holder from the sale of such Holder's Registrable Shares sold in connection with
such registration.

                  (c)    Promptly after receipt by an indemnified party under
this Section 1.9 of notice of the commencement of any action (including any
governmental action), such indemnified party will, if a claim in respect thereof
is to be made against any indemnifying party under this Section 1.9, deliver to
the indemnifying party a written notice of the commencement thereof and the
indemnifying party shall have the right to participate in, and, to the extent
the indemnifying party so desires, jointly with any other indemnifying party
similarly noticed, to assume the defense thereof with counsel mutually
satisfactory to the parties; PROVIDED, HOWEVER, that the failure of any
indemnified party to give notice as required under this Section 1.9 shall not
relieve the indemnifying party of its obligations under this Section 1.9 except
to the extent that the indemnifying party is adversely affected by such failure
to provide such notice. The indemnified party (together with all other
indemnified parties which may be represented without conflict by one counsel)
shall have the right to retain one separate counsel, with the fees and expenses
to be paid by the indemnifying party, if representation of such indemnified
party by the counsel retained by the indemnifying party would be inappropriate
due to actual or potential differing or conflicting interests between such
indemnified party and any other party represented by such counsel in such
proceeding.

                  (d)    If the indemnification provided for in this Section 1.9
is held by a court of competent jurisdiction to be unavailable to an indemnified
party with respect to any loss, liability, claim, damage, or expense referred to
therein, then the indemnifying party, in lieu of indemnifying such indemnified
party hereunder, shall contribute to the amount paid or payable by such
indemnified party as a result of such loss, liability, claim, damage, or expense
in such proportion as is appropriate to reflect the relative fault of the
indemnifying party on the one hand and of the indemnified party on the other in
connection with the statements or omissions that resulted in such loss,
liability, claim, damage, or expense as well as any other relevant equitable
considerations. The relative fault of the indemnifying party and of the
indemnified party shall be determined by reference to, among other things,
whether the untrue or alleged untrue statement of a material fact or the
omission to state a material fact relates to information that was supplied by
the indemnifying party or by the indemnified party and the parties' relative
intent, knowledge, access to information, and opportunity to correct or prevent
such statement or omission. The Company and the Holders agree that it would not
be just and equitable if contribution pursuant to this Section 1.9(d) were
determined by pro rata allocation or by any other method of allocation which
does not take account of the equitable considerations referred to above.
Notwithstanding the provisions of this Section 1.9(d), (i) in no case shall any
one Holder be liable or responsible for any amount in excess of the net proceeds
received by such Holder from the offering and sale of such Holder's Registrable
Securities pursuant to such registration statement which serves as the basis for
any claim under this Section 1.9 and (ii) the Company shall be liable and

                                        9
<Page>

responsible for any amount in excess of such net proceeds; provided, however,
that no person guilty of fraudulent misrepresentation (within the meaning of
Section 11(f) of the Act) shall be entitled to contribution from any person who
was not guilty of such fraudulent misrepresentation. Any party entitled to
contribution will, promptly after receipt of notice of commencement of any
action, suit or proceeding against such party in respect of which a claim for
contribution may be made against another party or parties under this Section
1.9(d), notify such party or parties from whom contribution may be sought, but
the omission so to notify such party or parties from whom contribution may be
sought shall not relieve such party from any other obligation it or they may
have thereunder or otherwise under this Section 1.9(d). No party shall be liable
for contribution with respect to any action, suit, proceeding or claim settled
without its prior written consent, which consent shall not be unreasonably
withheld, conditioned or delayed.

                  (e)    Notwithstanding the foregoing, to the extent that the
provisions with respect to indemnification and contribution contained in the
underwriting agreement entered into in connection with the underwritten public
offering which includes Registrable Shares registered hereunder are in conflict
with the foregoing provisions, the provisions in this Agreement shall control.

                  (f)    The obligations of the Company and Holders under this
Section 1.10 shall survive the termination of this Agreement and completion of
any offering of Registrable Securities in a registration statement under this
Section 1 and otherwise.

          1.10    REPORTS UNDER SECURITIES EXCHANGE ACT OF 1934. With a view to
making available to the Holders the benefits of Rule 144 promulgated under the
Act and any other rule or regulation of the SEC that may at any time permit a
Holder to sell securities of the Company to the public without registration or
pursuant to a registration on Form S-3, the Company agrees to:

                  (a)    make and keep current public information available, as
those terms are understood and defined in Rule 144 promulgated under the Act, at
all times after ninety (90) days after the effective date of the first
registration statement pursuant to a firm commitment underwriting filed by the
Company for the offering of its securities to the general public;

                  (b)    take such action, including the voluntary registration
of its Common Stock under Section 12 of the 1934 Act, as is necessary to enable
the Holders to utilize Form S-3 for the sale of the Holders' Registrable
Securities, such action to be taken as soon as practicable after the end of the
fiscal year in which the first registration statement filed by the Company for
the offering of its securities to the general public pursuant to a firm
commitment underwriting is declared effective;

                  (c)    file with the SEC in a timely manner all reports and
other documents required of the Company under the Act and the 1934 Act; and

                  (d)    furnish to any Holder, so long as the Holder owns any
Registrable Securities, forthwith upon request (i) a written statement by the
Company that it has complied with the reporting requirements of Rule 144
promulgated under the Act (at any time after ninety (90) days after the
effective date of the first registration statement filed by the Company), the
Act

                                       10
<Page>

and the 1934 Act (at any time after it has become subject to such reporting
requirements), or that it qualifies as a registrant whose securities may be
resold pursuant to Form S-3 (at any time after it so qualifies), (ii) a copy of
the most recent annual or quarterly report of the Company and such other reports
and documents so filed by the Company, and (iii) such other information as may
be reasonably requested in availing any Holder of any rule or regulation of the
SEC which permits the selling of any such securities without registration or
pursuant to such form.

          1.11    FORM S-3 REGISTRATION. In the event that the Company receives
a written request from any Holder that the Company effect a registration on Form
S-3 (or any successor form relating to secondary offerings) and any related
qualification or compliance with respect to all or a part of the Registrable
Securities owned by such Holder, the Company will:

                  (a)    promptly give written notice of the proposed
registration, and any related qualification or compliance, to all other Holders
in accordance with Section 5.5; and

                  (b)    as soon as practicable, effect such registration and
all such qualifications and compliances as may be so requested and as would
permit or facilitate the sale and distribution of all or a portion of such
Holder's or Holders' Registrable Securities as are specified in such request,
together with all or a portion of the Registrable Securities of any other Holder
or Holders joining in such request as are specified in a written request given
to the Company within twenty (20) days after receipt of such written notice from
the Company; PROVIDED, HOWEVER, that the Company shall not be obligated to
effect any such registration, qualification or compliance, pursuant to this
Section 1.11: (i) if Form S-3 is not available for such offering by the Holders;
(ii) if the Holders, together with the holders of any other securities of the
Company entitled to inclusion in such registration, propose to sell Registrable
Securities and such other securities (if any) at an aggregate price to the
public of less than $5,000,000; or (iii) if the Company shall furnish to the
Holders a certificate signed by the Chief Executive Officer of the Company
stating that in the good faith judgment of the Board of Directors of the
Company, it would be seriously detrimental to the Company and its stockholders
for such Form S-3 registration to be effected at such time, in which event the
Company shall have the right to defer the filing of the Form S-3 registration
statement for a period of not more than 45 days after receipt of the request of
the Holder or Holders under this Section 1.11, PROVIDED, HOWEVER, that the
Company shall not utilize this right to delay such registration on Form S-3 more
than once in any twelve (12) month period.

                  (c)    Subject to the foregoing, the Company shall file a
registration statement covering the Registrable Securities and other securities
so requested to be registered as expeditiously as possible after receipt of the
request or requests of the Holders. All expenses other than underwriting
discounts and commissions incurred in connection with registrations requested
pursuant to Section 1.11, including, without limitation, all registration,
filing and qualification fees, printers' and accounting fees, and the reasonable
fees and disbursements of one counsel for the selling Holders shall be borne by
the Company. Registrations effected pursuant to this Section 1.11 shall not be
counted as demands for registration or registrations effected pursuant to
Sections 1.2 or 1.3. The obligations of the Company under Section 1.4(a) through
1.4(l) shall apply to any registration pursuant to this Section 1.11.

                                       11
<Page>

          1.12    MARKET STAND-OFF AGREEMENT. Each Investor hereby agrees that,
during the period specified by the Company and an underwriter of Common Stock or
other securities of the Company following the effective date of a registration
statement of the Company filed under the Act (the "Time Period"), it shall not,
to the extent requested by the Company and such underwriter, directly or
indirectly sell, offer to sell, contract to sell, grant any option to purchase
or otherwise transfer or dispose of (other than to donees who agree to be
similarly bound) any securities of the Company held by it at any time during
such period except Common Stock included in such registration; PROVIDED,
HOWEVER, that:

                  (a)    such restriction shall be applicable only to the first
such registration statement of the Company filed with the SEC which covers
Common Stock (or other securities) to be sold on its behalf to the public in an
underwritten offering;

                  (b)    the Time Period shall not exceed 180 days;

                  (c)    all officers and directors of the Company and all other
holders of at least 1% of the shares of Common Stock outstanding immediately
prior to such registration enter into similar agreements; and

                  (d)    the Company shall use its reasonable efforts to enter
into an agreement with the managing underwriter of the offering of the Company's
Common Stock referenced in subsection (a) above to (i) allow periodic early
releases of portions upon certain specified events, and (ii) and to provide that
such early releases shall be on a pro rata basis for all parties subject to such
restriction on any securities of the Company.

     In order to enforce the foregoing covenant, the Company may impose stop
transfer instructions with respect to the Registrable Securities of each
Investor (and the shares or securities of every other person subject to the
foregoing restriction) until the end of such period.

     Notwithstanding the foregoing, the obligations described in this Section
1.12 shall not apply to a registration relating solely to employee benefit plans
on Form S-1 or Form S-8 or similar forms which may be promulgated in the future,
or a registration relating solely to a Commission Rule 145 transaction on Form
S-4 or Form S-5 or similar forms which may be promulgated in the future.

          1.13    TERMINATION OF REGISTRATION RIGHTS. No Holder shall be
entitled to exercise any right provided for in this Section 1 after seven (7)
years following the consummation of the sale of securities pursuant to a
registration statement filed by the Company under the Act in connection with the
initial firm commitment underwritten offering of its securities to the general
public.

          1.14    FUTURE ISSUANCES OF SECURITIES. Registration rights granted by
the Company in connection with the issuance of any securities after the date
hereof shall be no more favorable to the purchasers of such securities than the
registration rights granted herein to the Investors.

                                       12
<Page>

     2.   COVENANTS.

     2.1  DELIVERY OF FINANCIAL STATEMENTS. The Company shall deliver to each
Investor owning at least an aggregate of 100,000 shares of Series B Preferred
Stock, Series C Preferred Stock or Series D Preferred Stock:

                         (i)     as soon as practicable, but in any event within
ninety (90) days after the end of each fiscal year of the Company, a cash flow
statement for such fiscal year, an income statement for such fiscal year, a
balance sheet of the Company and statement of stockholder's equity as of the end
of such year (all on a consolidated basis), and a schedule as to the sources and
applications of funds for such year, such year-end financial reports to be in
reasonable detail, prepared in accordance with U.S. generally accepted
accounting principles ("GAAP") consistently applied, including all footnotes,
and audited and certified by independent public accountants of nationally
recognized standing selected by the Company;

                         (ii)    within 30 days after the end of each month
(other than the last month of any fiscal year), an unaudited balance sheet of
the Company as at the end of such month and unaudited statements of income and
of cash flows of the Company for such month and for the current fiscal year to
the end of such month, setting forth in comparative form the Company's projected
financial statements for the corresponding periods for the current fiscal year
prepared in accordance with U.S. generally accepted accounting principles,
consistently applied;

                         (iii)   as soon as practicable, but in any event thirty
(30) days prior to the end of each fiscal year, a budget for the next fiscal
year (prepared on a monthly basis) approved by the Company's Board of Directors
and, as soon as prepared, any other budgets or revised budgets prepared by the
Company.

                         (iv)    All rights of the Investors under this
Section 2.1 shall terminate upon the Company's Qualified Public Offering (as
defined below).

          2.2     RIGHT OF FIRST OFFER.

                  (a)    The Company 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 such case the Company shall have first
complied with this Section 2.2. The Company shall deliver to each Qualified
Investor a written notice of any proposal or intended issuance, sale or exchange
of Offered Securities containing the information specified in this Section
2.2(a) (the "Offer"), which shall: (i) identify and describe the Offered
Securities, (ii) describe the price and other terms upon which they are to be
issued, sold or exchanged, and the number or amount of the Offered Securities to
be issued, sold or exchanged, (iii) identify the persons or entities (if known)
to which or with which the Offered Securities are to be offered, issued, sold or
exchanged, and (iv) offer to issue and sell to or exchange with such Qualified
Investor such Qualified Investor's Basic Amount.

                  (b)    To accept an Offer, in whole or in part, a Qualified
Investor must deliver to the Company, on or prior to the date 30 days after the
date of delivery of the Offer, a notice of acceptance (the "Notice of
Acceptance") providing a representation letter certifying

                                       13
<Page>

that such Qualified Investor is an accredited investor within the meaning of
Rule 501 under the Act and indicating the portion of the Qualified Investor's
Basic Amount that such Qualified Investor elects to purchase and, if such
Qualified Investor shall elect to purchase all of its Basic Amount, the
additional portion of the Offered Securities attributable to the Basic Amounts
of Other Qualified Investors as such Qualified Investor indicates it will
purchase or acquire should other Qualified Investors subscribe for less than
their Basic Amounts (the "Undersubscription Amount") (if any) that such
Qualified Investor elects to purchase. If the Basic Amounts subscribed for by
all Qualified Investors are less than the total of all of the Basic Amounts
available for purchase, then each Qualified Investor who has set forth an
Undersubscription Amount in its Notice of Acceptance shall be entitled to
purchase, in addition to the Basic Amounts subscribed for, the Undersubscription
Amount it has subscribed for; provided, however, that if the Undersubscription
Amounts subscribed for exceed the difference between the total of all Basic
Amounts and the Basic Amounts subscribed for pursuant to this Section 2.2 (the
"Available Undersubscription Amount"), each Qualified Investor who has
subscribed for any Undersubscription Amount shall be entitled to purchase only
that portion of the Available Undersubscription Amount as the Undersubscription
Amount subscribed for by such Qualified Investor bears to the total
Undersubscription Amounts subscribed for by all Investors, subject to rounding
by the Board of Directors to the extent it deems reasonably necessary.

                  (c)    The Company shall have ninety (90) days from the
expiration of the thirty (30) day period within which the Notice of Acceptance
must be sent to the Company as set forth in Section 2.2(b) to issue, sell or
exchange all or any part of the Offered Securities not purchased by Investors
pursuant to this Section 2.2 (the "Refused Securities"), but only to the
offerees or purchasers described in the Offer (if so described therein) and only
upon terms and conditions (including, without limitation, unit prices and
interest rates) which are not more favorable, in the aggregate, to the acquiring
person or persons or less favorable to the Company than those set forth in the
Offer.

                  (d)    In the event the Company shall propose to sell less
than all the Refused Securities, then each Qualified Investor may, at its sole
option and in its sole discretion, reduce the number or amount of the Offered
Securities specified in its Notice of Acceptance to an amount that shall be not
less than the number or amount of the Offered Securities that the Qualified
Investor elected to purchase pursuant to Section 2.1(b) multiplied by a
fraction, (i) the numerator of which shall be the number or amount of Offered
Securities the Company actually proposes to issue, sell or exchange (including
Offered Securities to be issued or sold to Qualified Investors pursuant to
Section 2.2(b) prior to such reduction) and (ii) the denominator of which shall
be the original amount of the Offered Securities. In the event that any
Qualified Investor so elects to reduce the number or amount of Offered
Securities specified in its Notice of Acceptance, the Company may not issue,
sell or exchange more than the reduced number or amount of the Offered
Securities unless and until such securities have again been offered to the
Qualified Investor in accordance with Section 2.2(a).

                  (e)    Upon (i) the closing of the issuance, sale or exchange
of all or less than all of the Refused Securities or (ii) such other date agreed
to by the Company and Qualified Investors who have subscribed for a majority of
the Offered Securities subscribed for by the Qualified Investors, such Qualified
Investor or Qualified Investors shall acquire from the Company and the Company
shall issue to such Qualified Investor or Qualified Investors, the

                                       14
<Page>

number or amount of Offered Securities specified in the Notices of Acceptance,
as reduced pursuant to Section 2.2(d) if any of the Qualified Investors has so
elected, upon the terms and conditions specified in the Offer.

                  (f)    The purchase by the Qualified Investors of any Offered
Securities is subject in all cases to the preparation, execution and delivery by
the Company and the Qualified Investors of a purchase agreement relating to such
Offered Securities reasonably satisfactory in form and substance to the
Qualified Investors and their respective counsel.

                  (g)    Any Offered Securities not acquired by the Qualified
Investors or other persons in accordance with Section 2.2(c) may not be issued,
sold or exchanged until they are again offered to the Qualified Investors under
the procedures specified in this Agreement.

                  (h)    The rights of the Qualified Investors under this
Section 2.2 shall not apply to:

                         (i)     Common Stock issued pursuant to a stock split,
subdivision of the outstanding shares of Common Stock, or dividend or other
distribution payable in additional shares of Common Stock or other securities or
rights convertible into shares of Common Stock,

                         (ii)    shares of Common Stock issuable or issued to
employees, directors or consultants of this corporation pursuant to a stock
option plan or restricted stock plan approved by the Board of Directors of this
corporation at any time,

                         (iii)   up to an aggregate of 20,250 shares of Common
Stock issued upon the exercise of the outstanding warrants issued to Paul Clark,
Karen Elbing and Kristina Bieker-Brady,

                         (iv)    up to an aggregate of 15,750 shares of Common
Stock issued upon the exercise of an outstanding warrant issued to Silicon
Valley Bank,

                         (v)     up to an aggregate of 49,000 shares of Series C
Preferred Stock issued upon the exercise of outstanding warrants issued to
Comerica,

                         (vi)    up to an aggregate of 128,000 shares of Common
Stock issued upon the exercise of an outstanding warrant issued to Rockport
Venture Securities, LLC,

                         (vii)   the issuance of shares of capital stock of the
Company to financial lending institutions in connection with any borrowings
approved by the Board of Directors;

                         (viii)  the issuance of shares in connection with any
strategic alliances or strategic licensing agreements approved by the Board of
Directors;

                         (ix)    shares of Common Stock issued upon conversion
of the Series Preferred Stock,

                                       15
<Page>

                         (x)     shares of Common Stock issued or issuable in a
public offering before or in connection with which all outstanding shares of
Series Preferred Stock will be converted to Common Stock.

          2.3     INSPECTION. The Company shall permit each Investor who holds
not less than five percent (5%) of the total number of shares of the Common
Stock of the Company then outstanding (assuming full conversion and exercise of
all convertible or exercisable securities), subject to execution of reasonable
nondisclosure agreements (if appropriate), to visit and inspect the properties
of the Company, including its corporate and financial records, and to discuss
its business and finances with the officers of the Company, during normal
business hours following reasonable notice and as often as may be reasonably
requested.

          2.4     TERMINATION OF CERTAIN COVENANTS. The covenants set forth in
Sections 2.1, 2.2, and 2.3 shall terminate and be of no further force or effect
upon the consummation of the sale of equity securities pursuant to a
registration statement filed by the Company under the Act in connection with the
firm commitment underwritten offering of its equity securities to the general
public with proceeds to the Company of at least $40 million and a per share
price of at least $11.25 (subject to adjustment for any stock dividends,
combinations, splits, recapitalizations and similar events) ("Qualified Public
Offering").

          3.      COVENANTS.

                  3.1    NEGATIVE COVENANTS. The Company shall not, without the
approval of the Company's Board of Directors (or any committee of the Board of
Directors consisting of a majority of Preferred Directors (as defined below)),
including the approval of at least three directors who are designated as a
director by the Holders of Series B Preferred Stock, Series C Preferred Stock or
Series D Preferred Stock (the "Preferred Directors") pursuant to the Second
Amended and Restated Voting Agreement of even date herewith by and among the
Company and the Investors (as defined therein):

                  (a)    authorize and implement the Company's annual operating
and capital budgets, or make any material modifications thereto (for the
purposes of this Agreement, the approval of the Company's annual operating and
capital budget, as provided for in this section shall hereinafter be referred to
as the "Approved Budget");

                  (b)    pay bonuses to any senior executives not contemplated
in the Approved Budget or such senior executive's employment agreement;

                  (c)    enter into any employment agreement with any senior
executive;

                  (d)    enter into, or permit any subsidiary of the Company to
enter into, any lines of business that are not primarily related to the business
of the Company as conducted as of the date of this Agreement;

                  (e)    acquire, directly or indirectly (including through
a Company Subsidiary), all or substantially all of the properties, assets or
stock of any other company or entity;

                                       16
<Page>

                  (f)    incur any indebtedness, or permit any Company
Subsidiary to incur any indebtedness (other than indebtedness of Company
Subsidiaries owed to the Company), in excess of $1,000,000 in the aggregate,
unless provided for in the Approved Budget;

                  (g)    guarantee, or permit any Company Subsidiary to
guarantee, directly or indirectly, any indebtedness or obligations except for
trade accounts of any Company Subsidiary arising in the ordinary course of
business;

                  (h)    grant an exclusive license to any of the Company's
Proprietary Rights or Intellectual Property (as such terms are defined in the
Series D Convertible Preferred Stock Purchase Agreement of even date herewith by
and among the Company and the Investors (as defined therein) (the "Series D
Purchase Agreement"));

                  (i)    repay of any debt of the Company or repurchase or
cancel any of the securities of the Company, except that the Company may repay
up to $4 million of its obligations under equipment leases outstanding as of the
date hereof;

                  (j)    redeem, retire, purchase or acquire, directly or
indirectly, through subsidiaries or otherwise, any shares of the Company's
capital stock, other than the repurchase of shares of Common Stock from holders
upon termination of employment or service pursuant to agreements or plans
approved by the Board of Directors; and

                  (k)    other than as contemplated by this Agreement, other
than transactions in the ordinary course of business, enter into, after the date
of this Agreement, any transaction, including, without limitation, any loans or
extensions of credit or royalty agreements, with any officer, director or
affiliate of the Company or any subsidiary or any member of their respective
immediate families or any corporation or other entity directly or indirectly
affiliated with one or more of such officers, directors or members of their
immediate families; provided that the approval of any such transaction shall be
obtained in advance and from a majority of the disinterested members of the
Board of Directors.

          3.2     AFFIRMATIVE COVENANTS.

                  (a)    The Company shall maintain for a period of five years
after the date hereof term life insurance upon the life of Alexis Borisy in the
amount of $1,000,000, with the proceeds payable to the Company.

                  (b)    The Company shall require (i) all persons now or
hereafter employed by the Company and (ii) all independent contractors utilized
by the Company who have access to confidential or proprietary information of the
Company to enter into non-disclosure and assignment of inventions agreements
substantially in the form customarily used by the Company, a copy of which has
been provided to the Investors prior to the date hereof, and shall require all
employees who occupy or obtain a position of Associate Director or higher with
the Company (or a similar or comparable position within the Company), unless
otherwise agreed upon by a vote of the Company's Board of Directors (including a
majority of the Preferred Directors) whether now employed or hereafter employed
by the Company, to enter into non-competition and non-solicitation agreements in
the form customarily used by the Company, a

                                       17
<Page>

copy of which has been provided to the Investors prior to the date hereof, or
such other form as may be approved by the Board of Directors of the Company and
by a majority of the Preferred Directors or by any committee of the Board of
Directors consisting of a majority of Preferred Directors.

                  (c)    The Company agrees that it will not, without the prior
written consent of the holders of a majority of the Series Preferred Stock then
outstanding, terminate, amend or waive any rights under any inventions,
confidentiality, non-competition or restricted stock agreement between the
Company and any Founder (as defined in the Series D Purchase Agreement).

                  (d)    At the time any individual becomes a Management Member
(as defined in the Second Amended and Restated Co-Sale Agreement of even date
herewith by and between the Company, the Preferred Stockholders, the Management
Members and the Purchasers (each as defined therein) (the "Co-Sale Agreement"),
the Company shall promptly have such individual sign, and become a party as a
Management Member to the Co-Sale Agreement and the Company shall not issue any
certificates representing shares of the Company's stock issuable to a Management
Member until such time as such Management Member signs and becomes a party to
the Co-Sale Agreement.

                  (e)    The Company agrees that each fiscal year end audit
shall be performed by Ernst & Young or other nationally recognized accounting
firm approved by the Board of Directors.

                  (f)    Except as otherwise approved by the Compensation
Committee of the Board of Directors, from the date hereof all stock options
granted by the Company to Alexis Borisy, Michael A. Foley, Brent R. Stockwell,
Curtis T. Keith, other officers or directors of the Company or consultants shall
vest as follows: 25% on the first anniversary of the grant of the stock options
and 6.25% per quarter thereafter.

          3.3     TERMINATION. All covenants under this Section 3 shall
terminate upon the completion of a firm commitment underwritten initial public
offering of the Company's Common Stock with net proceeds to the Company of at
least $40 million and a price per share of at least $11.25 (subject to
adjustment for any stock dividends, combinations, splits, recapitalizations and
similar events).

          4.      DIRECTED SHARE PROGRAM.

                  (a)    In the event of an initial public offering of equity
securities of the Company (the "IPO"), the Company will establish, or cause the
managing underwriter to establish, a directed share program, consistent with
applicable laws, rules and regulations (including, without limitation, rules and
regulations promulgated by the SEC and the National Association of Securities
Dealers, Inc. (the "NASD")), pursuant to which the Investors, on a pro rata
basis in accordance with their ownership of Preferred Stock shall have the
option to purchase up to seven and one half percent (7.5%) of the securities
offered in the offering

                                       18
<Page>

(including securities offered in the over-allotment option) (the "Directed
Shares") at the initial offering price to the public. The Investors holding
Preferred Stock shall have a right of oversubscription with respect to the
Directed Shares such that if any Investor fails to purchase its pro rata portion
of the Directed Shares, the other Investors shall, among them, have the right to
purchase up to the balance of the Directed Shares not so purchased. If, as a
result thereof, such oversubscriptions exceed the total number of Directed
Shares available in respect of such oversubscription privilege, the
oversubscribing Investors shall be reduced with respect to their
oversubscriptions on a pro rata basis in accordance with their ownership of
Preferred Stock or as they may otherwise agree among themselves. Each Investor
shall have the right to transfer his right to buy any Directed Shares or any
part thereof to any Qualified Transferee. For purposes of this Agreement,
"Qualified Transferee" shall mean, with respect to any Investor, any person or
entity which, directly or indirectly, controls, is controlled by or is under
common control with such Investor, including, without limitation, any general
partner, officer or director of such Investor and any venture capital fund now
or hereafter existing which is controlled by one or more general partners of, or
shares the same management company as, such Investor.

                  (b)    Notwithstanding Section 4(a), if the SEC determines
that the sale of Directed Shares as contemplated therein would violate the
Securities Act, or if counsel for the Company determines that such sale would
otherwise violate applicable laws, rules or regulations (including, without
limitation, rules and regulations promulgated by the SEC and the NASD), the
Company may satisfy in full its obligations under Section 4(a) by offering the
Investors the option of purchasing unregistered shares of Common Stock in a
private offering in the amount that otherwise would have been offered as
Directed Shares either (i) prior to the IPO at a price to be negotiated in good
faith between the Investors and the Company, which price shall not exceed the
high point of the filing range of record at the SEC, or (ii) along side the IPO
at the IPO price to the public; provided, however, that if the SEC determines
that consummation of either alternative set forth above would violate the
Securities Act, be "integrated" with the IPO, or if counsel for the Company
determines that such alternative would otherwise violate applicable laws, rules
or regulations (including, without limitation, rules and regulations promulgated
by the SEC and the NASD), then the Company shall use its reasonable best efforts
to take such lawful action as shall most closely preserve the rights of the
Investors under this Section 4. Notwithstanding anything to the contrary in this
Section 4 or the Agreement contained, it is agreed and understood that the
Company shall not be required to satisfy its obligations hereunder by selling
registered and unregistered shares in excess of the maximum number of shares
that the Company is prepared to register in an IPO. For avoidance of doubt, in
the event, for whatever reason, the Company cannot satisfy its obligations
hereunder with shares registered in the IPO, then the number of shares
registered will be reduced on a one for one basis, by the number of unregistered
shares provided to the Investors. Nothing herein shall in any way effect the
right of the Investors to receive the full amount of the directed shares as
described above.

          5.      MISCELLANEOUS.

          5.1     SUCCESSORS. This Agreement shall inure to the benefit of and
be binding upon the parties hereto and their respective heirs, successors,
assigns, administrators, executors and other legal representatives.

                                       19
<Page>

          5.2     GOVERNING LAW.  This Agreement shall be governed by and
construed under the laws of the Commonwealth of Massachusetts without regard to
the principles of conflicts of law.

          5.3     COUNTERPARTS. This Agreement may be executed in any number of
counterparts (including, in the case of a purchaser of Series D Preferred Stock,
by means of a Financing Signature Page (as defined in the Series D Purchase
Agreement)), each of which shall be an original but all of which together shall
constitute one instrument.

          5.4     TITLES AND SUBTITLES. The titles and subtitles used in this
Agreement are used for convenience only and are not to be considered in
construing or interpreting this Agreement.

          5.5     NOTICES. All notices, requests, consents, and other
communications under this Agreement shall be in writing and shall be deemed
delivered (i) three business days after being sent by registered or certified
mail, return receipt requested, postage prepaid, (ii) one business day after
being sent via a reputable nationwide overnight courier service guaranteeing
next business day delivery or (iii) in the case of any Investor with an address
located outside the United States, three business days after being sent via a
reputable international courier service guaranteeing three business day
delivery, in each case to the intended recipient as set forth below:

     If to the Company, at 650 Albany Street, Boston, MA 02118, Attention:
President, or at such other address as may have been furnished in writing by the
Company to the other parties hereto, with a copy to Rubin & Rudman LLP, 50 Rowes
Wharf, Boston, MA 02110, Attention: Peter Finn, Esq.; or

     If to an Investor, at the address set forth on EXHIBIT A to this Agreement
for such Investor, or at such other address as may have been furnished in
writing by such Investor to the other parties hereto, provided, however, that
registered or certified mail shall not be used to provide notice to any such
Investor with an address located outside of the United States.

     Any party may give any notice, request, consent or other communication
under this Agreement using any other means (including, without limitation,
personal delivery, messenger service, telecopy, first class mail or electronic
mail), but no such notice, request, consent or other communication shall be
deemed to have been duly given unless and until it is actually received by the
party for whom it is intended. Any party may change the address to which
notices, requests, consents or other communications hereunder are to be
delivered by giving the other parties notice in the manner set forth in this
Section.

          5.6     ATTORNEY'S FEES. In the event that any suit or action is
instituted to enforce any provision in this Agreement, the prevailing party in
such dispute shall be entitled to recover from the losing party all fees, costs
and expenses of enforcing any right of such prevailing party under or with
respect to this Agreement, including without limitation, such reasonable fees
and expenses of attorneys and accountants, which shall include, without
limitation, all fees, costs and expenses of appeals.

                                       20
<Page>

          5.7     AMENDMENTS OR WAIVER. Any provision of this Agreement may be
amended or the observance thereof may be waived (either generally or
specifically and either retroactively or prospectively), only by an instrument
in writing executed by (a) the Company and (b) the holders of a majority of the
Registrable Securities then outstanding; provided that this Agreement may be
amended to add a new investor purchasing shares of Series D Preferred Stock from
the Company on or prior to March 31, 2004 as an Investor hereunder by an
instrument executed solely by the Company and such new investor and upon such
amendment Schedule A hereto shall be amended to add such new investor. Any
amendment or waiver so effected shall be binding upon the Company, each of the
other parties hereto and any assignee or successor of any such party.

          5.8     SEVERABILITY. In the event that one or more of the provisions
of this Agreement are held to be unenforceable under applicable law, such
provision shall be excluded from this Agreement and the balance of the Agreement
shall be interpreted as if such provision were so excluded and shall be
enforceable in accordance with its terms.

          5.9     AGGREGATION OF STOCK. All shares of Registrable Securities
held or acquired by affiliated entities or persons shall be aggregated together
for the purpose of determining the availability of any rights under this
Agreement.

          5.10    ENTIRE AGREEMENT.  This Agreement constitutes the full and
entire understanding and agreement between the parties regarding the subject
matters hereof.

          5.11    SPECIFIC PERFORMANCE. The parties hereto hereby declare that
it is impossible to measure in money the damages which will accrue to a party
hereto or to their heirs, personal representatives, or assigns by reason of a
failure to perform any of the obligations under this Agreement and agree that
the terms of this Agreement shall be specifically enforceable. If any party
hereto or his heirs, personal representatives, or assigns institutes any action
or proceeding to specifically enforce the provisions hereof, any person against
whom such action or proceeding is brought hereby waives the claim or defense
therein that such party or such personal representative has an adequate remedy
at law, and such person shall not offer in any such action or proceeding the
claim or defense that such remedy at law exists.

          5.12    WAIVER. No waivers of any breach of this Agreement extended by
any party hereto to any other party shall be construed as a waiver of any rights
or remedies of any other party hereto or with respect to any subsequent breach.

                [Remainder of the page left intentionally blank.]

                                       21
<Page>

     IN WITNESS WHEREOF, the parties hereto have executed this Investors' Rights
Agreement as of the date first above written.

                         COMPANY:

                             COMBINATORX, INCORPORATED
                             a Delaware corporation

                             By: /s/ Alexis Borisy
                                -----------------------------------------
                                Name: Alexis Borisy
                                Title: Chief Executive Officer and President,
                                       hereunder duly authorized

                         INVESTORS:

                             Each of the Investors who have executed a
                             counterpart signature page to this Agreement.

                 [SIGNATURE PAGE TO INVESTORS' RIGHTS AGREEMENT]

<Page>

                                   SCHEDULE A

                              SCHEDULE OF INVESTORS

NAME
AGTC Advisors Fund, L.P.
Alstertor Private Life GmbH & Co. KG
Applied Genomic Technology Capital Fund, L.P.
BIOVENTURES INVESTORS LIMITED PARTNERSHIP II
Boston Millennia Associates II Partnership
Boston Millennia Partners GmbH & Co. KG
Boston Millennia Partners II Limited Partnership
Boston Millennia Partners II-A Limited Partnership
Canaan Equity II Entrepreneurs LLC
Canaan Equity II L.P. (QP)
Canaan Equity II L.P.
CDIB BioScience Ventures I, Inc.
CDIB Biotech USA Investment, Co., Ltd.
CDIB Bioventures, Inc.
China Development Industrial Bank Inc.
Easton Hunt Capital Partners, L.P.
Foundation Medical Partners, L.P.
The Global Life Science Ventures Fonds II GmbH & Co. KG
The Global Life Science Ventures Fund II Limited Partnership
Jacob Goldfield
JPMORGAN Chase Bank as Custodian to the BVCF IV, L.P.
Novartis BioVentures Ltd.
POSCO BioVentures I, L.P.
Private Life BioMed AG, Hamburg
Dr. Seth Rudnick
Strategic Advisors Fund Limited Partnership
TL Ventures V Interfund L.P.
TL Ventures V L.P.
The Yasuda Enterprise Development II, Limited Partnership

<Page>

                            COMBINATORX, INCORPORATED

                OMNIBUS CONSENT, WAIVER, AND AMENDMENT AGREEMENT

     This Omnibus Consent, Waiver, and Amendment Agreement ("Agreement") is made
effective as of August 5, 2004 ("Effective Date"), by and among CombinatoRx,
Incorporated, a Delaware corporation (the "Company"), and those of the Company's
stockholders and directors as have executed a counterpart signature page to this
Agreement.

ENLARGEMENT OF THE BOARD OF DIRECTORS

     WHEREAS, the Company and certain holders (the "Founders") of the Company's
$0.001 par value common stock ("Common Stock") and certain holders of the
Company's $0.001 par value preferred stock (the "Investors"), established an
eight (8) person Board of Directors elected as set forth in that certain Second
Amended and Restated Voting Agreement dated February 18, 2004 as amended by that
certain Omnibus Consent and Amendment dated effective March 16, 2004 (as
amended, the "Voting Agreement").

     WHEREAS, the Company's Board of Directors, Investors, and Founders wish to
enlarge the Board of Directors to nine (9) members and to elect Frank Haydu as a
Director.

     WHEREAS, the decision to enlarge the Board of Directors requires an
amendment to (i) the Voting Agreement and (ii) the Company's Fourth Amended and
Restated Certificate of Incorporation filed February 18, 2004 as amended by a
Certificate of Amendment filed March 18, 2004 (as amended, the "Certificate").

DEBT FINANCINGS WITH WARRANT COVERAGE

     WHEREAS, in connection with a working capital credit facility with
Lighthouse Capital Partners V, L.P. ("LCP-V"), the Company will issue warrants
to LCP-V and its affiliated fund, Lighthouse Capital Partners IV, L.P.
("LCP-IV") (LCP-V and LCP-IV, collectively "Lighthouse"), to acquire (i) up to
90,772 shares of the Company's $0.001 par value Series D Preferred Stock (the
"Preferred Stock") and (ii) up to an additional 84,288 shares of Preferred stock
depending on the amount actually advanced by Lighthouse to the Company.

     WHEREAS, in connection with a working capital loan with General Electric
Capital Corporation ("GECC"), the Company will issue a warrant to GECC to
acquire up to 15,561 shares of Preferred Stock. For the purposes of this
Agreement, the term "Warrants" shall refer collectively to the aforesaid
warrants to be issued to LCP-IV, LCP-V, and GECC.

     WHEREAS, the possible addition of Lighthouse, GECC, and/or their respective
designees as stockholders could require the addition of such persons to (i) the
Company's Voting Agreement; (ii) that certain Second Amended and Restated
Investors' Rights Agreement dated as of February 18, 2004 as amended by that
certain Omnibus Consent and Amendment dated effective March 16, 2004 (as
amended, the "Investors' Rights Agreement"); and (iii) that certain Second
Amended and Restated Co-Sale Agreement dated as of February 18, 2004 as amended
by

                                        1
<Page>

that certain Omnibus Consent and Amendment dated effective March 16, 2004 (as
amended, the "Co-Sale Agreement").

     WHEREAS, as a condition to the financings with Lighthouse and GECC, the
Company has agreed to grant each of LCP-IV, LCP-V, and GECC registration rights
with respect to the shares of the Company's Common Stock issuable upon
conversion of the Preferred Stock purchasable pursuant to their respective
Warrants, such registration rights to be the same as those available to the
Investors pursuant to the Investors' Rights Agreement.

     WHEREAS, pursuant to the Investors' Rights Agreement, each of the Investors
has a right (the "Right of First Offer") to be first offered such Investor's pro
rata share of any new securities offered by the Company and the Investors'
Rights Agreement may be amended or any provision thereof waived by an instrument
in writing executed by the Company and by the holders of a majority of the
"Registrable Securities" held by the Investors.

     WHEREAS, the undersigned Investors, representing at least a majority of the
"Registrable Securities" held by the Investors, desire to waive their aforesaid
right of first offer in connection with the Warrants.

     WHEREAS, as a condition to the financing with Lighthouse, the Company has
agreed to grant LCP-V the right to purchase up to $500,000 worth of the stock
the Company issues in its next private equity financing which right requires the
Investors to agree to cut back their Right of First Offer to the extent LCP-V
purchases up to $500,000 worth of the stock the Company issues in its next
private equity financing.

     NOW, THEREFORE, in consideration of the mutual covenants contained herein
and other good and valuable consideration, the receipt and sufficiency of which
are hereby acknowledged, the parties hereto agree to the terms set forth below.

SECTION 1.  AMENDMENT OF THE SECOND AMENDED AND RESTATED VOTING AGREEMENT.

     The Company and the Founders and Investors executing a counterpart to this
Agreement hereby agree that effective as of the Effective Date, the Voting
Agreement shall be and hereby is amended substantively as follows:

            (a)  The first sentence of Article 1.2 of the Voting Agreement is
     hereby deleted in its entirety, and there is hereby substituted the
     following:

                 "The Company's Board of Directors shall consist of nine (9)
            directors."

            (b)  Article 1.2 (f) of the Voting Agreement is hereby deleted in
     its entirety, and there is hereby substituted the following:

                                        2
<Page>

                 "(f)    To cause the election to the Company's Board of
            Directors as directors three (3) persons mutually designated by the
            directors elected pursuant to Section 1(a) through 1(e) of this
            Agreement, provided that the directors elected pursuant to this
            Section 1(f) shall not be serving as employees of the Company at the
            time of such election, initially Richard H. Aldrich, Richard Pops
            and Frank Haydu."

     and

            (c)  The last sentence of Article 3.5 is hereby deleted in its
     entirety, and there is hereby substituted the following:

            "Notwithstanding the foregoing, this Agreement may be amended to add
            a new investor purchasing shares of Series D Preferred Stock from
            the Company pursuant to any of the following:

                 (i)     on or prior to March 31, 2004;

                 (ii)    those certain warrants to purchase up to a maximum
                 aggregate amount of 87,530 shares of Series D Preferred Stock
                 originally issued by the Company to Lighthouse Capital Partners
                 IV, L.P. in or about August 2004;

                 (iii)   those certain warrants to purchase up to a maximum
                 aggregate amount of 87,530 shares of Series D Preferred Stock
                 originally issued by the Company to Lighthouse Capital Partners
                 V, L.P. in or about August 2004; or

                 (iv)    that certain warrant to purchase up to a maximum amount
                 of 15,561 shares of Series D Preferred Stock originally issued
                 to General Electric Capital Corporation in or about August
                 2004,

            as an Investor hereunder by an instrument executed solely by the
            Company and such new investor and upon such amendment Schedule A
            hereto shall be amended to add such new investor."

SECTION 2.  AMENDMENT OF THE SECOND AMENDED AND RESTATED INVESTORS' RIGHTS
AGREEMENT.

     The Company and the Investors executing a counterpart to this Agreement
hereby agree that effective as of the Effective Date the Investors' Rights
Agreement shall be and hereby is amended substantively as follows:

     (a)    a new Section 2.2(i) shall be added to read as follows:

                                        3
<Page>

          "(i) Notwithstanding any other provision of this Agreement, in the
          event that all of the following conditions apply:

               (i)     the Company delivers an Offer to the Investors pursuant
               to Section 2.2(a);

               (ii)    Lighthouse Capital Partners V, L.P. or its successor
               ("LCP-V") is eligible to exercise and wishes to exercise the
               right (the "Lighthouse Right") to purchase securities of the
               Company as set forth in section 6.8 of that certain "Loan and
               Security Agreement" dated August ___, 2004 by and between the
               Company and LCP-V; and

               (iii)   the Investors deliver Notices of Acceptance to the
               Company pursuant to Section 2.2(b) for such amount of the Offered
               Securities as would not permit LCP-V to fully exercise the
               Lighthouse Right,

          then the amounts of Offered Securities each Investor shall be entitled
          to purchase shall be cut back in the following manner to the minimum
          extent necessary to enable LCP-V to exercise the Lighthouse Right:

               (x)     first, the Undersubscription Amount of each Investor
               specifying an Undersubscription Amount shall be cut back pro rata
               in relation to the Undersubscription Amounts specified by all
               other Investors who specified an Undersubscription Amount; and

               (y)     second, if the adjustments made pursuant to paragraph
               2.2(i)(x) were insufficient, the Basic Amount of each Investor
               who delivered a Notice of Acceptance shall be cut back pro rata
               in relation to the Basic Amounts specified by all other Investors
               who delivered a Notice of Acceptance."

          and

     (b)  the current version of Section 5.7 is deleted in its entirety and
replaced with the following new Section 5.7:

          "5.7 AGREEMENTS OR WAIVER. Any provision of this Agreement may be
          amended or the observance thereof may be waived (either generally or
          specifically and either retroactively or prospectively),

                                        4
<Page>

            only by an instrument in writing executed by (a) the Company and (b)
            the holders of a majority of the Registrable Securities then
            outstanding; provided that this Agreement may be amended to add a
            new investor purchasing shares of Series D Preferred Stock from the
            Company pursuant to any of the following:

               (i)     on or prior to March 31, 2004;

               (ii)    those certain warrants to purchase up to a maximum
               aggregate amount of 87,530 shares of Series D Preferred Stock
               originally issued by the Company to Lighthouse Capital Partners
               IV, L.P. in or about August 2004;

               (iii)   those certain warrants to purchase up to a maximum
               aggregate amount of 87,530 shares of Series D Preferred Stock
               originally issued by the Company to Lighthouse Capital Partners
               V, L.P. in or about August 2004; or

               (iv)    that certain warrant to purchase up to a maximum amount
               of 15,561 shares of Series D Preferred Stock originally issued to
               General Electric Capital Corporation in or about August 2004,

            as an Investor hereunder by an instrument executed solely by the
            Company and such new investor and upon such amendment Schedule A
            hereto shall be amended to add such new investor. Any amendment or
            waiver so effected shall be binding upon the Company, each of the
            other parties hereto and any assignee or successor of any such
            party.

SECTION 3.  AMENDMENT OF THE SECOND AMENDED AND RESTATED CO-SALE AGREEMENT.

     The Company and the Founders, Investors, and Management Member (as defined
in the Co-Sale Agreement) executing a counterpart to this Agreement hereby agree
that effective as of the Effective Date the Co-Sale Agreement shall be and
hereby is amended substantively as follows:

            (a)  The last sentence of Article 11.6 is hereby deleted in its
     entirety, and there is hereby substituted the following:

            "Notwithstanding the foregoing, this Agreement may be amended to add
            a new investor purchasing shares of Series D Preferred Stock from
            the Company pursuant to any of the following:

                 (i)     on or prior to March 31, 2004;

                                        5
<Page>

                 (ii)    those certain warrants to purchase up to a maximum
                 aggregate amount of 87,530 shares of Series D Preferred Stock
                 originally issued by the Company to Lighthouse Capital Partners
                 IV, L.P. in or about August 2004;

                 (iii)   those certain warrants to purchase up to a maximum
                 aggregate amount of 87,530 shares of Series D Preferred Stock
                 originally issued by the Company to Lighthouse Capital Partners
                 V, L.P. in or about August 2004; or

                 (iv)    that certain warrant to purchase up to a maximum amount
                 of 15,561 shares of Series D Preferred Stock originally issued
                 to General Electric Capital Corporation in or about August
                 2004,

            as an Investor hereunder by an instrument executed solely by the
            Company and such new investor and upon such amendment Schedule A
            hereto shall be amended to add such new investor."

SECTION 4.  CONFIRMATION OF CONTINUED EFFECT; AUTHORITY TO MAKE CHANGES.

     (a)    The Company and the Founders and Investors executing a counterpart
signature page to this Agreement agree that the Voting Agreement as modified
herein shall remain in full force and effect as so modified. The Company and the
Investors executing a counterpart signature page to this Agreement agree that
the Investors' Rights Agreement as modified herein shall remain in full force
and effect as so modified. The Company and the Founders, Investors, and
Management Member executing a counterpart signature page to this Agreement agree
that the Co-Sale Agreement as modified herein shall remain in full force and
effect as so modified.

     (b)    In order to reduce the costs associated with the closing of the
transactions described in this Agreement, the undersigned hereby give the
authority to the officers of the Company to make non-substantive changes to the
amendments proposed in this Agreement without first seeking the consent of the
Company's stockholders and directors.

SECTION 5.  WAIVER OF PARTICIPATION RIGHT.

     The Investors executing a counterpart signature page below for themselves
and, in accordance with the provisions of Section 5.7 of the Investors' Rights
Agreement, for all other Investors hereby waive the right of first offer (and
any related or corresponding notice requirement) contained in the Investors'
Rights Agreement to purchase any of the Warrants, any of the Preferred Stock
issuable upon exercise of the Warrants, or any of the Common Stock issuable upon
conversion of such aforesaid Preferred Stock.

                                        6
<Page>

SECTION 5.  CONSENT IN LIEU OF A MEETING.

     Pursuant to sections 141(f), 228, and 242 of the Delaware General Company
Law and the Company's By-laws, the undersigned stockholders (including
Stockholders holding the requisite number of shares of any class or series
entitled to a class vote, as appropriate) and the Directors hereby consent to
the following resolutions without the necessity of calling or holding a formal
meeting of the Stockholders and Directors and direct the Secretary of the
Company ("Secretary") to file a copy of this Agreement with the minutes of the
Company:

     APPROVAL OF MATTERS RELATED TO THIS OMNIBUS CONSENT, WAIVER, AND AMENDMENT
AGREEMENT

     RESOLVED: That, it is in the best interests of the Company to enlarge the
               Board of Directors to nine (9) members.

     RESOLVED: That effective upon the filing of the Certificate of Amendment
               (as hereinafter defined), Frank Haydu is hereby elected as a
               Director of the Company to hold office until the earlier of his
               resignation, death, or replacement.

     RESOLVED: That, the Company is authorized to enter into, and the officers
               of the Company each acting alone on behalf of the Company and in
               their respective capacities as officers of the Company, are
               authorized, empowered, and directed to amend and execute and
               deliver this Omnibus Consent, Waiver, and Amendment Agreement.

     AMENDMENT OF FOURTH AMENDED AND RESTATED CERTIFICATE OF INCORPORATION

     RESOLVED: That, in connection with and as a condition to the enlargement of
               the Board of Directors to nine (9) members and in connection with
               the issuance of the Warrants, the Company is hereby authorized to
               further amend its Fourth Amended and Restated Certificate of
               Incorporation filed with the Secretary of State of the State of
               Delaware on February 18, 2004 ("Fourth Certificate") by filing
               with the Secretary of State of the State of Delaware that certain
               Certificate of Amendment of the Fourth Amended and Restated
               Certificate of Incorporation substantively in the form of that
               attached hereto as Exhibit 1 ("Certificate of Amendment"), such
               Certificate of Amendment providing for the enlargement of the
               Board of Directors to nine (9) members and for the increase in
               the number of shares of Common Stock and Preferred Stock that the
               Company is authorized to issue, and the resolutions set forth in
               the Certificate of Amendment at paragraph 3 are hereby approved
               and adopted as written therein.

     RESOLVED: That, in connection with the foregoing resolution, the officers
               of the Company, each acting alone on behalf of the Company and in
               their respective capacities as officers of the Company, are
               authorized, empowered, and directed to execute the Certificate of
               Amendment and file it with the

                                        7
<Page>

               Secretary of State of the State of Delaware along with the
               payment of the appropriate filing fee out of the Company's funds.

THE REMAINDER OF THIS PAGE HAS BEEN INTENTIONALLY LEFT BLANK

                                       8<Page>

                                                                   Exhibit 10.18

                            COMBINATORX, INCORPORATED

                     OMNIBUS AMENDMENT AND WAIVER AGREEMENT

     This Omnibus Amendment and Waiver Agreement ("Agreement") is made effective
as of December 8, 2004 ("Effective Date") by and among CombinatoRx,
Incorporated, a Delaware corporation (the "Company"), and the following holders
of the Company's stock and warrants (collectively, the "Holders") as have
executed a counterpart signature page to this Agreement.

     WHEREAS, the Company is planning on consummating the sale of shares of its
$0.001 par value per share common stock ("Common Stock") pursuant to a
registration statement filed or to be filed by the Company under the federal
Securities Act of 1933, as amended, in connection with an underwritten offering
of such shares to the general public (the "Public Offering");

     WHEREAS, the Company is a party to each of the following agreements and
each of the Holders is a party to one or more of the following agreements:

     (a)  that certain Second Amended and Restated Investors' Rights Agreement
     dated as of February 18, 2004, as amended by that certain Omnibus Consent,
     Waiver, and Amendment Agreement dated August 5, 2004 (as amended, the
     "Investors' Rights Agreement");

     (b)  that certain Second Amended and Restated Voting Agreement dated as of
     February 18, 2004, as amended by that certain Omnibus Consent, Waiver, and
     Amendment Agreement dated August 5, 2004 (as amended, the "Voting
     Agreement");

     (c)  that certain Second Amended and Restated Co-Sale Agreement dated as of
     February 18, 2004, as amended by that certain Omnibus Consent, Waiver, and
     Amendment Agreement dated August 5, 2004 (as amended, the "Co-Sale
     Agreement" and with the Investors' Rights Agreement and the Voting
     Agreement, collectively, the "Stockholder Agreements"); and

     (d)  that certain Registration Rights Agreement ("Registration Rights
     Agreement") entered into as of April 25, 2001 by and between the Company
     and Silicon Valley Bank ("SVB");

     WHEREAS, various provisions of the Stockholders Agreements are triggered by
or may apply to a transaction in which the Company sells shares of its capital
stock (whether or not pursuant to a registered underwritten offering to the
general public);

     WHEREAS, certain of the Holders possess rights to register shares of Common
Stock pursuant to the Investors' Rights Agreement or pursuant to the
Registration Rights Agreement;

     WHEREAS, the Company may effect a stock dividend, combination, split,
recapitalization, or similar capital reorganization (a "Reorganization") prior
to the Public Offering;

                                        1
<Page>

     WHEREAS, various provisions of the Stockholders Agreements refer to
specific numbers of shares which need to be changed in connection with any
Recapitalization; and

     WHEREAS, the Company and the undersigned Holders desire to ensure the
orderly consummation of the Public Offering and the orderly administration of
the terms and provisions of the Stockholder Agreements pending and following the
Public Offering and any Recapitalization;

     NOW, THEREFORE, in consideration of the foregoing and the terms and
provisions set forth below, the sufficiency of which consideration is
acknowledged by all parties to be adequate, the parties executing below agree to
the terms and provisions set forth below.

SECTION 1.   AMENDMENT OF STOCKHOLDER AGREEMENTS.

(a)  Pursuant to section 5.7 of the Investors' Rights Agreement, effective as of
the Effective Date, the Company and those of the Holders who are parties to the
Investors' Rights Agreement, being the holders of a majority of the "Registrable
Securities" (as that term is defined in the Investors' Rights Agreement) hereby
amend the Investors' Rights Agreement as follows:

     (i)     the first paragraph of section 2.1 of the Investors' Rights
     Agreement is hereby amended by adding after the reference to "100,000" the
     following passage "(as adjusted for any stock dividends, combinations,
     splits, recapitalizations, and the like with respect to such shares)";

     (ii)    sections 2.2(h)(iii), (iv), (v), and (vi) of the Investors' Rights
     Agreement are deleted in their entirety and there are hereby substituted
     the following paragraphs:

          "(iii)  up to an aggregate of 20,250 (as adjusted for any stock
          dividends, combinations, splits, recapitalizations, and the like with
          respect to such shares) shares of Common Stock issued upon the
          exercise of the outstanding warrants issued to Paul Clark, Karen
          Elbing and Kristina Bieker-Brady,

          "(iv)   up to an aggregate of 17,534 (as adjusted for any stock
          dividends, combinations, splits, recapitalizations, and the like with
          respect to such shares) shares of Common Stock or 15,750 (as adjusted
          for any stock dividends, combinations, splits, recapitalizations, and
          the like with respect to such shares) shares of Series B Preferred
          Stock upon the exercise of an outstanding warrant issued to Silicon
          Valley Bank,

          "(v)    up to an aggregate of 49,000 (as adjusted for any stock
          dividends, combinations, splits, recapitalizations, and the like with
          respect to such shares) shares of Common Stock or Series C Preferred
          Stock issued upon the exercise of outstanding warrants issued to
          Comerica Incorporated (formerly Comerica Bank - California and
          Comerica Bank),

          "(vi)   up to an aggregate of 128,000 (as adjusted for any stock
          dividends, combinations, splits, recapitalizations, and the like with
          respect

                                        2
<Page>

          to such shares) shares of Common Stock issued upon the exercise of an
          outstanding warrant issued to Rockport Venture Securities, LLC,";

     (iii)   section 2.4 of the Investors' Rights Agreement is deleted in its
     entirety and there is hereby substituted the following paragraph:

          "2.4    TERMINATION OF CERTAIN COVENANTS. The covenants set forth in
          Sections 2.1, 2.2, and 2.3 shall terminate and be of no further force
          or effect upon the consummation of the sale of equity securities
          pursuant to a registration statement filed by the Company under the
          Act in connection with an underwritten public offering of its equity
          securities with a price per share as approved by a committee of the
          Company's Board of Directors designated as the "Pricing Committee"
          ("Qualified Public Offering").";

     (iv)    section 3.3 of the Investors' Rights Agreement is deleted in its
     entirety and there is hereby substituted the following paragraph:

          "3.3    TERMINATION. All covenants under this Section 3 shall
          terminate upon the completion of a Qualified Public Offering."; and

     (v)     section 5.7 of the Investors' Rights Agreement is deleted in its
     entirety and there is hereby substituted the following paragraphs:

          "5.7    AGREEMENTS OR WAIVER. Any provision of this Agreement may be
          amended or the observance thereof may be waived (either generally or
          specifically and either retroactively or prospectively), only by an
          instrument in writing executed by (a) the Company and (b) the holders
          of a majority of the Registrable Securities then outstanding; provided
          that this Agreement may be amended to add a new investor purchasing
          shares of Common Stock or Series D Preferred Stock from the Company
          pursuant to any of the following:

                  (i)    those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners IV, L.P. on September 7, 2004;

                  (ii)   those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners V, L.P. on September 7, 2004; or

                  (iii)  that certain warrant to purchase Common Stock or Series
                  D Preferred Stock originally issued to General Electric
                  Capital Corporation on September 15, 2004,

                                        3
<Page>

          as an Investor hereunder by an instrument executed solely by the
          Company and such new investor and upon such amendment Schedule A
          hereto shall be amended to add such new investor. Any amendment or
          waiver so effected shall be binding upon the Company, each of the
          other parties hereto and any assignee or successor of any such party."

(b)  Pursuant to section 3.5 of the Voting Agreement, effective as of the
Effective Date, the Company and those of the Holders who are parties to the
Voting Agreement, being the holders of a majority of the "Investor Shares" (as
that term is defined in the Voting Agreement) and the holders of a majority of
the "Founder Shares" (as that term is defined in the Voting Agreement) hereby
amend the Voting Agreement as follows:

     (i)     section 2 of the Voting Agreement is deleted in its entirety and
     there is hereby substituted the following paragraph:

          "2.     TERMINATION. This Agreement shall continue in full force and
          effect from the date hereof through the date of the closing of an
          underwritten public offering of the common stock of the Company,
          $0.001 par value per share (the "Common Stock") pursuant to a
          registration statement filed with the Securities and Exchange
          Commission, and declared effective under the Securities Act of 1933,
          as amended, in which the price per share of Common Stock to the public
          is that amount approved by a committee of the Company's Board of
          Directors designated as the "Pricing Committee"."; and

     (ii)    the last sentence of section 3.5 of the Voting Agreement is deleted
     in its entirety and there is hereby substituted the following sentence:

          "Notwithstanding the foregoing, this Agreement may be amended to add a
          new investor purchasing shares of Common Stock or Series D Preferred
          Stock from the Company pursuant to any of the following:

                  (i)    those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners IV, L.P. on September 7, 2004;

                  (ii)   those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners V, L.P. on September 7, 2004; or

                  (iii)  that certain warrant to purchase Common Stock or Series
                  D Preferred Stock originally issued to General Electric
                  Capital Corporation on September 15, 2004,

                                        4
<Page>

          as an Investor hereunder by an instrument executed solely by the
          Company and such new investor and upon such amendment Schedule A
          hereto shall be amended to add such new investor."

(c)  Pursuant to section 11.6 of the Co-Sale Agreement, effective as of the
Effective Date, the Company and those of the Holders who are parties to the
Co-Sale Agreement, being the holders of a majority of the voting power of all
"Shares" then held by "Preferred Stockholders" (as those terms are defined in
the Co-Sale Agreement) and the holders of a majority of the voting power of all
"Shares" held by "Founders" and "Management Members" (as those terms are defined
in the Co-Sale Agreement) hereby amend the Co-Sale Agreement as follows:

     (i)     section 9.1 of the Co-Sale Agreement is deleted in its entirety and
     there is hereby substituted the following paragraph:

          "9.1    This Agreement shall terminate in its entirety upon the
          closing of the Company's underwritten public offering of the Common
          Stock pursuant to a Form S-1 (or any successor form) which has been
          declared effective by the Securities and Exchange Commission and in
          which the Common Stock is sold to the public at a per share price
          approved by a committee of the Company's Board of Directors designated
          as the "Pricing Committee" (the "Qualified Public Offering")."

     (ii)    the last sentence of section 11.6 is deleted in its entirety and
     there is hereby substituted the following sentence:

          "Notwithstanding the foregoing, this Agreement may be amended to add a
          new investor purchasing shares of Common Stock or Series D Preferred
          Stock from the Company pursuant to any of the following:

                  (i)    those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners IV, L.P. on September 7, 2004;

                  (ii)   those certain warrants to purchase Common Stock or
                  Series D Preferred Stock originally issued by the Company to
                  Lighthouse Capital Partners V, L.P. on September 7, 2004; or

                  (iii)  that certain warrant to purchase Common Stock or Series
                  D Preferred Stock originally issued to General Electric
                  Capital Corporation on September 15, 2004,

             as a Preferred Stockholder hereunder by an instrument executed
             solely by the Company and such new investor and upon such amendment
             Schedule A hereto shall be amended to add such new investor."; and

                                        5
<Page>

     (iii)   section 11.7 is hereby amended by adding after the reference to
     "100,000" the following passage "(as adjusted for any stock dividends,
     combinations, splits, recapitalizations, and the like with respect to such
     shares)".

SECTION 2.   WAIVERS.

(a)  Pursuant to section 5.7 of the Investors' Rights Agreement, the Company and
those of the Holders who are parties to the Investors' Rights Agreement, being
the holders of a majority of the "Registrable Securities" (as that term is
defined in the Investors' Rights Agreement), for themselves and for all other
parties to the Investors' Rights Agreement, hereby waive the following rights
under the Investors' Rights Agreement solely in connection with the Public
Offering and the shares of Common Stock issuable by the Company in connection
with the Public Offering:

     (i)     those rights of first offer and other rights described in
     Section 2.2 of the Investors' Rights Agreement; and

     (ii)    those rights with respect to the "Directed Share Program" and other
     rights described in Section 4 of the Investors' Rights Agreement.

(b)  Pursuant to section 2.1 of the Registration Rights Agreement, SVB hereby
waives its rights as described in Section 1.2 of the Registration Rights
Agreement to include in the Public Offering shares of the Company's capital
stock held by or issuable to SVB.

SECTION 3.   CONFIRMATION OF CONTINUED EFFECT; AUTHORITY TO MAKE CHANGES.

(a)  The Company and the Holders executing a counterpart signature page to this
Agreement agree that the Investors' Rights Agreement as modified herein shall
remain in full force and effect as so modified, the Voting Agreement as modified
herein shall remain in full force and effect as so modified, and the Co-Sale
Agreement as modified herein shall remain in full force and effect as so
modified.

(b)  In order to reduce the costs associated with the foregoing amendments and
waivers, and the consummation of the Public Offering and any Recapitalization,
the undersigned Holders hereby give the authority to the officers of the Company
to make non-substantive changes to the amendments described in this Agreement
without first seeking the consent of the Company's stockholders and directors.

SECTION 4.   MISCELLANEOUS PROVISIONS.

(a)  This Agreement shall be governed by and construed under the laws of the
Commonwealth of Massachusetts without regard to the principles of conflicts of
laws.

(b)  This Agreement shall inure to the benefit of and be binding upon the
parties hereto and their respective heirs, successors, assigns, administrators,
executors, and other legal representatives.

                                        6
<Page>

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

THE REMAINDER OF THIS PAGE HAS BEEN INTENTIONALLY LEFT BLANK

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