<Page>

                                                                  Exhibit 10.5

THIS WARRANT AND THE SHARES ISSUABLE HEREUNDER HAVE NOT BEEN REGISTERED UNDER
THE SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT BE SOLD, PLEDGED OR
OTHERWISE TRANSFERRED WITHOUT AN EFFECTIVE REGISTRATION THEREOF UNDER SUCH ACT
OR PURSUANT TO RULE 144 OR AN OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE
CORPORATION AND ITS COUNSEL THAT SUCH REGISTRATION IS NOT REQUIRED.

                            WARRANT TO PURCHASE STOCK

<Table>
          <S>                       <C>
          Corporation:              COMBINATORX, INCORPORATED, a Delaware corporation
          Number of Shares:         35,000
          Class of Stock:           Series C Convertible Preferred Stock
          Initial Exercise Price:   $3.75 per share
          Issue Date:               September 10, 2002
          Expiration Date:          September 9, 2009 (Subject to Section 4.1)
</Table>

     THIS WARRANT CERTIFIES THAT, for good and valuable consideration, the
receipt of which is hereby acknowledged, COMERICA BANK - CALIFORNIA or its
assignee ("Holder") is entitled to purchase the number of fully paid and
nonassessable shares of the class of securities (the "Shares") of the
corporation (the "Company") at the initial exercise price per Share (the
"Warrant Price") all as set forth above and as adjusted pursuant to Article 2 of
this warrant, subject to the provisions and upon the terms and conditions set
forth in this warrant.

ARTICLE 1. EXERCISE.

     1.1     METHOD OF EXERCISE. Holder may exercise this warrant by delivering
this warrant and a duly executed Notice of Exercise in substantially the form
attached as Appendix 1 to the principal office of the Company. Unless Holder is
exercising the conversion right set forth in Section 1.2, Holder shall also
deliver to the Company a check for the aggregate Warrant Price for the Shares
being purchased.

     1.2     CONVERSION RIGHT. In lieu of exercising this warrant as specified
in Section 1.1, Holder may from time to time convert this warrant, in whole or
in part, into a number of Shares determined by dividing (a) the aggregate fair
market value of the Shares or other securities otherwise issuable upon exercise
of this warrant minus the aggregate Warrant Price of such Shares by (b) the fair
market value of one Share. The fair market value of the Shares shall be
determined pursuant to Section 1.3.

     1.3     FAIR MARKET VALUE. If the Shares are traded regularly in a public
market, the fair market value of the Shares shall be the closing price of the
Shares (or the closing price of the Company's stock into which the Shares are
convertible) reported for the business day immediately before Holder delivers
its Notice of Exercise to the Company. If the Shares are not regularly traded in
a public market, the Board of Directors of the Company shall determine fair
market value in its reasonable good faith judgment.

     1.4     DELIVERY OF CERTIFICATE AND NEW WARRANT. Promptly after Holder
exercises or converts this warrant, the Company shall deliver to Holder
certificates for the Shares acquired and, if this warrant has not been fully
exercised or converted and has not expired, a new warrant representing the
Shares not so acquired.

     1.5     REPLACEMENT OF WARRANTS. On receipt of evidence reasonably
satisfactory to the Company of the loss, theft, destruction or mutilation of
this warrant and, in the case of loss, theft or destruction, on delivery of an
indemnity agreement reasonably satisfactory in form and amount to the Company
or, in the case of mutilation, on surrender and cancellation of this warrant,
the Company at its expense shall execute and deliver, in lieu of this warrant, a
new warrant of like tenor.

<Page>

     1.6     REPURCHASE ON SALE, MERGER, OR CONSOLIDATION OF THE COMPANY.

             1.6.1  "ACQUISITION." For the purpose of this warrant,
"Acquisition" means any sale, license, or other disposition of all or
substantially all of the assets (including intellectual property) of the
Company, or any reorganization, consolidation, or merger of the Company where
the holders of the Company's securities before the transaction beneficially own
less than 50% of the outstanding voting securities of the surviving entity after
the transaction.

             1.6.2   ASSUMPTION OF WARRANT. Upon the closing of any Acquisition
the Company shall cause the successor entity to assume the obligations of this
warrant, provided that the Holder has not otherwise exercised this warrant in
full, and this warrant shall be exercisable for the same securities, cash, and
property as would be payable for the Shares issuable upon exercise of the
unexercised portion of this warrant as if such Shares were outstanding on the
record date for the Acquisition and subsequent closing. The Warrant Price shall
be adjusted accordingly.

ARTICLE 2.ADJUSTMENTS TO THE SHARES.

     2.1     STOCK DIVIDENDS, SPLITS, ETC. If, after the Issue Date, the Company
declares or pays a dividend on its Series C Convertible Preferred Stock,
subdivides the outstanding Series C Convertible Preferred Stock into a greater
amount of Series C Convertible Preferred Stock, then upon exercise of this
warrant, for each Share acquired, Holder shall receive, without cost to Holder,
the total number of Series C Convertible Preferred Stock to which Holder would
have been entitled had Holder owned the Series C Convertible Preferred Stock of
record as of the date the dividend or subdivision occurred.

     2.2     RECLASSIFICATION, EXCHANGE OR SUBSTITUTION. Upon any
reclassification, exchange, substitution, or other event that results in a
change of the number and/or class of the securities issuable upon exercise or
conversion of this warrant, Holder shall be entitled to receive, upon exercise
or conversion of this warrant, the number and kind of securities and property
that Holder would have received for the Shares if this warrant had been
exercised immediately before such reclassification, exchange, substitution, or
other event. Such an event shall include any automatic conversion of the
outstanding or issuable securities of the Company of the same class or series as
the Shares to common stock pursuant to the terms of the Company's Certificate of
Incorporation upon the closing of a registered public offering of the Company's
common stock. The Company or its successor shall promptly issue to Holder a new
warrant for such new securities or other property. The new warrant shall provide
for adjustments which shall be as nearly equivalent as may be practicable to the
adjustments provided for in this Article 2 including, without limitation,
adjustments to the Warrant Price and to the number of securities or property
issuable upon exercise of the new warrant. The provisions of this Section 2.2
shall similarly apply to successive reclassifications, exchanges, substitutions,
or other events.

     2.3     ADJUSTMENTS FOR COMBINATIONS, ETC. If the outstanding Shares are
combined or consolidated, by reclassification or otherwise, into a lesser number
of shares, the Warrant Price shall be proportionately increased. If the
outstanding Shares are combined or consolidated, by reclassification or
otherwise, into a greater number of shares, the Warrant Price shall be
proportionately decreased.

     2.4     NO IMPAIRMENT. The Company shall not, by amendment of its
Certificate of Incorporation or through a reorganization, transfer of assets,
consolidation, merger, dissolution, issue, or sale of securities or any other
voluntary action, avoid or seek to avoid the observance or performance of any of
the terms to be observed or performed under this warrant by the Company, but
shall at all times in good faith assist in carrying out all the provisions of
this Article 2 and in taking all such action as may be necessary or appropriate
to protect Holder's rights under this Article against impairment.

     2.5     CERTIFICATE AS TO ADJUSTMENTS. Upon each adjustment of the Warrant
Price, the Company at its expense shall promptly compute such adjustment, and
furnish Holder with a certificate of its Chief Financial Officer setting forth
such adjustment and the facts upon which such adjustment is based. The Company
shall, upon written request, furnish Holder a certificate setting forth the
Warrant Price in effect upon the date thereof and the series of adjustments
leading to such Warrant Price.

                                       2
<Page>

ARTICLE 3.REPRESENTATIONS AND COVENANTS OF THE COMPANY.

     3.1     REPRESENTATIONS AND WARRANTIES. The Company hereby represents and
warrants to the Holder as follows:

             (a)    All Shares which may be issued upon the exercise of the
purchase right represented by this warrant, and all securities, if any, issuable
upon conversion of the Shares, shall, upon issuance, be duly authorized, validly
issued, fully paid and nonassessable, and free of any liens and encumbrances
except for restrictions on transfer provided for herein or under applicable
federal and state securities laws.

             (b)    The Company's capitalization table attached to this warrant
is true and complete as of the Issue Date.

     3.2     NOTICE OF CERTAIN EVENTS. If the Company proposes at any time (a)
to declare any dividend or distribution upon its common stock, whether in cash,
property, stock, or other securities and whether or not a regular cash dividend;
(b) to offer for subscription pro rata to the holders of any class or series of
its stock any additional shares of stock of any class or series or other rights;
(c) to effect any reclassification or recapitalization of common stock; or (d)
to merge or consolidate with or into any other corporation, or sell, lease,
license, or convey all or substantially all of its assets, or to liquidate,
dissolve or wind up, then, in connection with each such event, the Company shall
give Holder (1) at least 20 days prior written notice of the date on which a
record will be taken for such dividend, distribution, or subscription rights
(and specifying the date on which the holders of common stock will be entitled
thereto) or for determining rights to vote, if any, in respect of the matters
referred to in (a) and (b) above; and (2) in the case of the matters referred to
in (c) and (d) above at least 20 days prior written notice of the date when the
same will take place (and specifying the date on which the holders of common
stock will be entitled to exchange their common stock for securities or other
property deliverable upon the occurrence of such event).

     3.3     INFORMATION RIGHTS. So long as the Holder holds this warrant and/or
any of the Shares, the Company shall deliver to the Holder (a) promptly after
mailing, copies of all communiques to the shareholders of the Company, (b)
within ninety (90) days after the end of each fiscal year of the Company, the
annual audited financial statements of the Company certified by INDEPENDENT
public accountants of recognized standing and (c) within forty-five (45) days
after the end of each of the first three quarters of each fiscal year, the
Company's quarterly, unaudited financial statements.

     3.4     REGISTRATION UNDER SECURITIES ACT OF 1933, AS AMENDED. The Company
agrees that the Shares or, if the Shares are convertible into common stock of
the Company, such common stock, shall be subject to the registration rights set
forth on EXHIBIT A.

ARTICLE 4.MISCELLANEOUS.

     4.1     TERM: NOTICE OF EXPIRATION. This warrant is exercisable in whole or
in part, at any time and from time to time on or before the Expiration Date set
forth above; provided, however, that if the Company completes its initial public
offering within the three-year period immediately prior to the Expiration Date,
the Expiration Date shall automatically be extended until the third anniversary
of the effective date of the Company's initial public offering. If this warrant
has not been exercised prior to the Expiration Date, this warrant shall be
deemed to have been automatically exercised on the Expiration Date by "cashless"
conversion pursuant to Section 1.2.

     4.2     LEGENDS. This warrant and the Shares (and the securities issuable,
directly or indirectly, upon conversion of the Shares, if any) shall be
imprinted with a legend in substantially the following form:

THIS SECURITY HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS
AMENDED, AND MAY NOT BE SOLD, PLEDGED OR OTHERWISE TRANSFERRED WITHOUT AN
EFFECTIVE REGISTRATION THEREOF UNDER SUCH ACT OR PURSUANT TO RULE 144 OR AN
OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE CORPORATION AND ITS COUNSEL
THAT SUCH REGISTRATION IS NOT REQUIRED.

                                       3
<Page>

     4.3     COMPLIANCE WITH SECURITIES LAWS ON TRANSFER. This warrant and the
Shares issuable upon exercise of this warrant (and the securities issuable,
directly or indirectly, upon conversion of the Shares, if any) may not be
transferred or assigned in whole or in part without compliance with applicable
federal and state securities laws by the transferor and the transferee
(including, without limitation, the delivery of investment representation
letters and legal opinions reasonably satisfactory to the Company). The Company
shall not require Holder to provide an opinion of counsel if the transfer is to
an affiliate of Holder or if there is no material question as to the
availability of current information as referenced in Rule 144(c), Holder
represents that it has complied with Rule 144(d) and (e) in reasonable detail,
the selling broker represents that it has complied with Rule 144(f), and the
Company is provided with a copy of Holder's notice of proposed sale.

     4.4     TRANSFER PROCEDURE. Subject to the provisions of Section 4.3,
Holder may transfer all or part of this warrant or the Shares issuable upon
exercise of this warrant (or the securities issuable, directly or indirectly,
upon conversion of the Shares, if any) by giving the Company notice of the
portion of the warrant being transferred setting forth the name, address and
taxpayer identification number of the transferee and surrendering this warrant
to the Company for reissuance to the transferee(s) (and Holder, if applicable);
PROVIDED, HOWEVER, that Holder may transfer all or part of this warrant to its
affiliates, including, without limitation, Comerica Incorporated, at any time
without notice to the Company, and such affiliate shall then be entitled to all
the rights of Holder under this warrant and any related agreements, and the
Company shall cooperate fully in ensuring that any stock issued upon exercise of
this warrant is issued in the name of the affiliate that exercises the warrant.
The terms and conditions of this warrant shall inure to the benefit of, and be
binding upon, the Company and the holders hereof and their respective permitted
successors and assigns. The Company shall have the right to refuse to transfer
any portion of this warrant to any person who directly competes with the
Company, unless the Company is filing financial information with the SEC
pursuant to the Securities Exchange Act of 1934.

     4.5     NOTICES. All notices and other communications from the Company to
the Holder, or vice versa, shall be deemed delivered and effective when given
personally or mailed by first-class registered or certified mail, postage
prepaid, at such address as may have been furnished to the Company or the
Holder, as the case may be, in writing by the Company or such Holder from time
to time. All notices to the Holder shall be addressed as follows:

                    Comerica Bank - California
                    Attn: Warrant Administrator
                    Technology and Life Sciences Division
                    P.O. Box 7279
                    San Francisco, CA 94120-7279

     4.6     WAIVER. This warrant and any term hereof may be changed, waived,
discharged or terminated only by an instrument in writing signed by the party
against which enforcement of such change, waiver, discharge or termination is
sought.

     4.7     ATTORNEYS' FEES. In the event of any dispute between the parties
concerning the terms and provisions of this warrant, the party prevailing in
such dispute shall be entitled to collect from the other party all costs
incurred in such dispute, including reasonable attorneys' fees.

     4.8     GOVERNING LAW. This warrant shall be governed by and construed in
accordance with the laws of the State of California, without giving effect to
its principles regarding conflicts of law.

                                        COMBINATORX, INCORPORATED


                                        By:/s/ Edward J. Davis
                                        ----------------------------------------
                                        Name: Edward J. Davis
                                        Title: Executive Vice President and
                                        Chief Financial Officer
                                        Hereunto Duly Authorized

                                       4
<Page>

                                   APPENDIX 1

                               NOTICE OF EXERCISE

     1.      The undersigned hereby elects to purchase _______________ shares of
the _______________ stock of COMBINATORX, INCORPORATED pursuant to the terms of
the attached warrant, and tenders herewith payment of the purchase price of such
shares in full.

     2.      The undersigned hereby elects to convert the attached warrant into
shares in the manner specified in the warrant. This conversion is exercised with
respect to _______________ of the shares covered by the warrant.

     [STRIKE PARAGRAPH THAT DOES NOT APPLY.]

     3.      Please issue a certificate or certificates representing said shares
in the name of the undersigned or in such other name as is specified below:

             Comerica Bank - California
             Attn: Warrant Administrator
             Technology and Life Sciences Division
             P.O. Box 7279
             San Francisco, CA 94120-7279

             OR Registered Assignee

     4.      The undersigned represents it is acquiring the shares solely for
its own account and not as a nominee for any other party and not with a view
toward the resale or distribution thereof except in compliance with applicable
securities laws.

COMERICA BANK - CALIFORNIA or Registered
Assignee


-------------------------------------
(Signature)


-------------------------------------
(Date)

                                       5
<Page>

                                    EXHIBIT A

                               REGISTRATION RIGHTS

     The Shares (if common stock), or the common stock issuable upon conversion
of the Shares, shall be deemed "registrable securities" or otherwise entitled to
"piggy back" registration rights in accordance with the terms of the following
agreement (the "Agreement") between the Company and its investor(s):

     First Amended and Restated Investors' Rights Agreement dated as of
September 10, 2002 by and among the Company and the Series C Investors.

     The Company agrees that no amendments will be made to the Agreement, which
would have an adverse impact on Holder's registration rights thereunder without
the consent of Holder. By acceptance of the Warrant to which this EXHIBIT A is
attached, Holder shall be deemed to be a party to the Agreement.

                                       6

<Page>

COMERICA BANK - CALIFORNIA                  Five Palo Alto Square, Suite 800
                                            3000 El Camino Real
                                            Palo Alto, CA 94306

                                            Technology & Life Sciences Division

                                          November 13, 2002

Combinatorx, Inc.
650 Albany St.
Boston, MA 02118

              RE: NOTIFICATION OF ASSIGNMENT

Dear Sir/Madam,

       This notice is to inform you that the Warrant (the "Warrant") issued
9/10/02 by Combinatorx, Inc. to Comerica Bank - California ("Bank") has been
assigned by Bank to Comerica Incorporated, ("Comerica") per section 4.4 of
the Warrant. I have been designated as the Warrant Administrator for both
Bank and Comerica Incorporated to ensure that all notices or other
communications from your company regarding the Warrant is properly handled
through Comerica Incorporated.

      Please note the following addresses where notifications or
correspondence should be delivered:

                 Comerica Incorporated
                 c/o TLS/Administration
                 Attn: Warrant Administrator
                 P.O. Box 7279
                 San Francisco, CA 94120-7279
                 Fax: (650) 846-6830

       If you have any questions pertaining to the above, please do not
hesitate to contact me at (650) 846-6823. I look forward to working with you.


                                           Sincerely,

                                           /s/ Bridget Lim
                                           ----------------
                                           Bridget Lim
                                           Warrant Administrator