Document:

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                                                                 Exhibit 10.27

September 15, 2004

Eric McAllister, M.D.
5 Bobby Jones Lane
Coto de Caza, CA 92679

Dear Eric:

On behalf of CombinatoRx, Incorporated ("the Company"), I am pleased to offer
you the position of Senior Vice President of Clinical Development, reporting to
Jan Lessem, M.D., EVP & Chief Medical Officer.

Your job responsibilities in this position will include the following, which the
Company may modify at any time:

     -    Design, implement and monitor clinical studies of compounds designated
          for clinical development.
     -    Develop protocols and case report forms, which will provide adequate
          efficacy and safety information for Phases 1 to 3 of clinical trials.
     -    Interact with data management personnel to plan data entry and
          analysis; recruit/screen/select competent investigators; organize
          investigators' meetings; assure that Good Clinical Practices (GCPs)
          are followed; assure timely completion of studies; monitor data for
          safety and efficacy trends by reviewing clinical data; and write
          clinical reports upon completion or termination of studies (in
          cooperation with statistical staff).
     -    Review requests for results of Investigational New Drugs (IND)
          studies, and provides input for pharmacokinetics and pre-clinical
          studies.
     -    Prepare clinical portions of INDs, New Drug Applications (NDAs) and
          Biological License Applications (BLAs), including protocols,
          investigator brochures, medical reports, efficacy and safety
          summaries, scientific rationales and benefit/risk ratios.
     -    Plan clinical programs and develop a timetable, budget and resource
          analysis for clinical programs and personnel administration.
     -    Establish and maintain relationships with alliance partners, external
          companies, investigators and opinion leaders to optimize performance
          on clinical trial activities.
     -    Prepare manuscripts for technical journals and makes presentations at
          scientific meetings
     -    Other appropriate responsibilities.

2. EFFECTIVE DATE: The effective date of your employment with the Company will
be on or about November 1, 2004. Your employment with the Company will be
at-will, meaning that you will not be obligated to remain employed by the
Company for any specified period of time; likewise, the Company will not be
obligated to continue your employment for any specific period and may terminate
your employment at any time, with or without cause.

3. COMPENSATION: From the effective date of your employment your base pay will
be $10,416.67 (equivalent to $250,000 annually), paid twice per month. During
the period beginning January 1, 2005, your base pay will be $10,833.34
(equivalent to $260,000 annually). You will also be entitled to a signing bonus
of $32,500.00 which will be paid with your first paycheck.

Further, in accordance with the Company's Stock Option Plan (the "Plan"), and
Incentive Stock Option Grant Agreement (the "Agreement"), you are hereby granted
an Incentive Stock Option (the "Option") to purchase one hundred thousand
(100,000) shares of the Company's Common Stock at an exercise price of Fifty
(50 CENTS) cents per Share in accordance with the terms and conditions of the
Company's Stock Option Plan. The shares will vest over a four year period as
will be specified in the Agreement. In addition, we provide benefits that are
described in the section following.

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SEPTEMBER 15, 2004
-- Page 2 of 3 --

PERFORMANCE BONUS: Upon recommendation of the President/CEO and based on the
Company's financial and cash position and your contribution to the Company's
achievement of its annual goals, the Company may, in its discretion, award an
annual performance bonus of up to twenty five (25%) percent of your then annual
base compensation.

RELOCATION EXPENSE REIMBURSEMENT: To assist you in relocating to the Greater
Metropolitan Area ("Boston"), the Company will reimburse you for up to $35,000
for reasonable moving expenses associated with the move of your household goods
and furniture to the Greater Boston Metropolitan Area, as approved in advance by
the Company.

Additionally, the Company will reimburse you for two (2) house-hunting trips for
your spouse and reasonable costs of temporary housing for up to a period of six
(6) months, up to $24,000.00, as approved in advance by the Company.

4. BENEFITS: You will be eligible for the Company's standard benefits package.
Benefits include participation in a company sponsored health care plan, dental
plan, life insurance, short term disability insurance, and long term disability
insurance. You will also be eligible for a Company-matched 401(k) plan upon
employment. In addition to your compensation, you will be entitled to four (4)
weeks vacation earned on a pro-rata basis. Standard paid holidays will also be
observed. The Company, however, reserves the right to modify its employee
benefit programs.

5. SEVERANCE: In the event that the company elects to terminate your employment
without cause, you then will be entitled to receive your base compensation and
benefits for a period of six months from the date of termination.

6. CHANGE OF CONTROL. If a Change of Control (as defined below) occurs and,
within two (2) years following such Change of Control, the Company terminates
the Employee's employment other than for Cause, then, the Company (A) shall
provide the Employee six (6) months of severance pay, at the rate of the Base
Salary in effect immediately prior to the termination, payable in a single lump
sum within ten (10) business days following termination of employment; (B) shall
pay the premium cost of the Employee's participation in the Company's group
medical and dental plans for a period of six (6) months following the date of
termination, provided that the Employee is entitled to continue such
participation under applicable law and plan terms; and (C) shall cause to become
vested on the date of termination 100% of the options granted pursuant to
Section 3 hereof or otherwise which remain unvested on that date and the
Employee shall be entitled to not less than ninety (90) days following the date
of termination to exercise all or any portion of such options.

In the event that it is determined that any payments or benefits provided by the
Company to the Employee or for his benefit, either under this Agreement or
otherwise, will be subject to the excise tax imposed by section 4999 of the
Internal Revenue Code or any successor provision ("section 4999"), the Employee
may elect either to pay such excise tax or to have such payments and benefits
reduced to the extent necessary so that he shall not be liable for any such
excise tax.

"Change of Control" means the occurrence hereafter of (i) a sale, merger or
consolidation after which securities possessing more than fifty (50%) percent of
the total combined voting power of the Company's outstanding securities have
been transferred to or acquired by a Person or Persons different from the
Persons who held such percentage of the total combined voting power immediately
prior to such transaction; (ii) the sale, transfer or other disposition of all
or substantially all of the Company's assets to one or more Persons (other than
a wholly owned subsidiary of the Company or a parent company whose stock
ownership after the transaction is the same as the Company's ownership before
the transaction), or (iii) an acquisition, merger or similar transaction or a
divestiture of a substantial portion of the Company's business after which the
Employee's role is not substantially the same as such role prior to the
transaction.

7. EMPLOYMENT ELIGIBILITY VERIFICATION: Please note that all persons employed in
the United States are required to complete an Employment Eligibility
Verification Form (Form I-9) on the first day of employment

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SEPTEMBER 15, 2004
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and submit an original document or documents that establish identity and
employment eligibility within three business days of employment. This offer is
contingent upon your being able to verify that you can legally work in the U.S.

8. COMPETITION AND CONFIDENTIALITY: During the term of your employment, you
agree that you will not engage in any activity that is directly or indirectly
competitive with the Company. Upon your separation from the Company, you agree
to return to the Company all documents or property of the Company, or
reproductions of any such documents or property, developed by you or in your
possession.

In connection with your employment, you will be required to sign the Company's
Standard Confidential Information and Inventions Assignment Agreement (the
"Invention Agreement"), a copy of which is attached with this Letter Agreement.

Please indicate that you are in agreement with the above by signing the enclosed
copy of this Letter Agreement and the attached Invention Agreement, and
returning these to Ms. Melinda Austin, CombinatoRx, Inc., 650 Albany Street,
Boston, MA 02118.

We are all very enthusiastic about your joining us and have the highest
expectation of your contributions!

                                   Sincerely,

/s/ Alexis Borisy                                  /s/ Jan Lessem
---------------------------                        ---------------------------
Alexis Borisy                                      Jan Lessem, M.D.
President and CEO                                  EVP & Chief Medical Officer
CombinatoRx, Incorporated                          CombinatoRx, Incorporated

The within Letter Agreement and attached Invention Agreement are hereby
acknowledged, accepted and agreed to:

/s/ Eric McAllister                                 Date: 16 SEPT. 2004
-------------------------------------------         -----------------------
Eric McAllister, M.D.<Page>

                                                                 Exhibit 10.28

                            COMBINATORX, INCORPORATED

                               FOUNDER'S AGREEMENT

     This Founder's Agreement (this "Agreement") is made and entered into as of
this 26th day of January, 2001, by and between CombinatoRx, Incorporated, a
Delaware corporation (the "Company") and Alexis Borisy (the "Founder").

                                    RECITALS

     WHEREAS, the Founder is now the owner of 9,500 shares of Common Stock of
the Company of which 2,375 shares have vested and are not subject to the
Repurchase Option (as defined below) and of which 7,125 shares (the "Shares")
are subject to the Repurchase Option pursuant to the terms of this Agreement.

     WHEREAS, the parties desire to enter into this Agreement in connection
with, and as a condition precedent to, the issuance and sale of shares of the
Company's Series B preferred stock to certain investors.

     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:

     1.   REPURCHASE OPTION.

          (a)    In the event that the Founder's employment with or services to
the Company are terminated other than as a result of a Termination Event before
all of the Shares are released from the Repurchase Option of the Company (as
provided in Section 2), the Company shall have, upon the date of such
termination (as reasonably fixed and determined by the Company), an irrevocable,
exclusive option (the "Repurchase Option") for a period of ninety (90) days from
such dated to repurchase all or any portion of the Unreleased Shares (as defined
in Section 2) at such time, at the original purchase price per share (the
"Repurchase Price"). The Repurchase Option shall be exercised by the Company by
written notice to the Founder or the Founder's executor (with a copy to the
Escrow Holder) and, at the Company's option, (i) by delivery to the Founder or
the Founder's executor with such notice of a check in the amount of the
Repurchase Price for the Shares being repurchased, (ii) by cancellation by the
Company of an amount of the Founder's indebtedness to the Company equal to the
Repurchase Price for the Shares being repurchased or (iii) by a combination of
(i) and (ii) so that the combined payment and cancellation of indebtedness
equals such Repurchase Price. Upon delivery of such notice and the payment of
the Repurchase Price as described above, the Company shall become the legal and
beneficial owner of the Shares being repurchased and all rights and interests
therein or relating thereto, and the Company shall have the right to retain and
transfer to its own name the number of Shares being repurchased by the Company.
A "Termination Event" shall mean any of the following events: (x) the death of
the Founder, (y) the Founder's election to terminate his employment with the
Company as a direct result of the Company's material reduction in the

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nature of the Founder's responsibilities regarding his employment position with
the Company or (z) the Company's election to terminate the Founder's employment
with the Company other than in connection with any of the following relating to
the Founder: (1) conviction of, the indictment for, or the entering of a guilty
plea or plea of no contest with respect to, a felony, any act involving moral
turpitude, or a misdemeanor where imprisonment is a possible punishment, (2)
commission of any act of theft, fraud or dishonesty, (3) improper disclosure of
the Company's confidential or proprietary information, (4) any action involving
moral turpitude which has a detrimental effect on the Company's reputation or
business, (5) failure or inability to perform any reasonably assigned duties
after written notice from the Company of, and a reasonable opportunity to cure,
such failure or inability, (6) any breach of this Agreement or any employment,
consulting, advisory or other agreement with the Company, (7) a course of
conduct amounting to gross incompetence, (8) chronic and unexcused absenteeism,
(9) unlawful appropriation of a business opportunity, or (10) misconduct in
connection with the performance of any duties or responsibilities, including,
without limitation, misappropriation of funds or property of the Company,
securing or attempting to secure personally any profit in connection with any
transaction entered into on behalf of the Company, misrepresentation to the
Company, or any violation of law or regulations on Company premises or to which
the Company is subject.

     2.   RELEASE OF SHARES FROM REPURCHASE OPTION.

          (a)    One thirty-sixth (1/36) of the Shares shall be released from
the Repurchase Option on the last day of each full calendar month following
January 26, 2001 until all the Shares have been released from the Repurchase
Option provided that, except as set forth in the immediately following sentence,
in each case that the Founder's services as an employee of or consultant to the
Company have not been terminated prior to the date of any such release. In the
event that a Termination Event has occurred, all of the Unreleased Shares shall
be immediately released from the Company's Repurchase Option.

          (b)    Any of the Shares which have not yet been released from the
Repurchase Option are referred to herein as "Unreleased Shares." The Shares
which have been released from the Repurchase Option shall be delivered to the
Founder at the Founder's request.

          (c)    This Agreement shall not confer upon the Founder any right with
respect to continuation of employment by the Company, nor shall it interfere
with or affect in any manner the right or power of the Company, or a parent or
subsidiary of the Company, to terminate the Founder's employment at any time or
for any reason, with or without cause, which right is hereby reserved.

     3.   RESTRICTION ON TRANSFER. Except for the escrow described in Section 4
or the transfer of the Shares to the Company or its assignees as contemplated by
this Agreement, none of the Shares or any beneficial interest therein shall be
transferred, encumbered or otherwise disposed of in any way until the release of
such Shares from the Repurchase Option in accordance with the provisions of this
Agreement.

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     4.   ESCROW OF SHARES.

          (a)    The Shares shall be held by Rubin and Rudman LLP (the "Escrow
Holder"), along with a stock assignment executed by the Founder in blank, until
the expiration of the Repurchase Option as set forth above.

          (b)    The Escrow Holder is hereby directed to permit transfer of the
Shares only in accordance with this Agreement or instructions signed by both
parties. In the event further instructions are desired by the Escrow Holder, the
Escrow Holder shall be entitled to rely upon directions executed by a majority
of the authorized number of the Company's Board of Directors. The Escrow Holder
shall have no liability for any act or omission hereunder while acting in good
faith in the exercise of the Escrow Holder's own judgment.

          (c)    If the Company or any assignee exercises the Repurchase Option
hereunder, the Escrow Holder, upon receipt of written notice of such option
exercise from the proposed transferee, shall take all steps necessary to
accomplish such transfer.

          (d)    When the Repurchase Option has been exercised or expires
unexercised or a portion of the Shares has been released from such Repurchase
Option, upon Founder's request the Escrow Holder shall promptly cause a new
certificate to be issued for such released Shares and shall deliver such
certificate to the Founder.

          (e)    Subject to the terms hereof, the Founder shall have all the
rights of a stockholder with respect to the Shares while they are held in
escrow, including, without limitation, the right to vote the Shares and receive
any dividends declared thereon. If, from time to time during the term of the
Repurchase Option, there in any stock dividend, stock split or other change in
the Shares, any and all new, substituted or additional securities to which the
Founder is entitled by reason of the Founder's ownership of the Shares subject
to the Repurchase Option shall be immediately subject to this escrow, deposited
with the Escrow Holder and included thereafter as "Shares" for purposes of this
Agreement and the Repurchase Option.

     5.   MARKET STAND-OFF AGREEMENT. The Founder hereby agrees that, during the
period of duration 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 Securities Act of 1933, as
amended, he 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 him at
any time during such period except Common Stock included in such registration.

     6.   LEGENDS. The share certificate evidencing the Shares issued hereunder
shall be endorsed with the following legends:

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          (a)    "These securities have not been registered under the Securities
Act of 1933, as amended. They may not be sold, offered for sale, pledged or
hypothecated in the absence of a registration statement in effect with respect
to the securities under Act or an opinion of counsel satisfactory to the Company
that such registration is not required or unless sold pursuant to Rule 144 of
such Act."

          (b)    "The shares represented by this certificate may be transferred
only in accordance with the terms of an agreement between the Company and the
stockholder, a copy of which is on file with the Secretary of the Company."

          (c)    Any legend required by applicable securities laws including,
without limitation, any legend required by the General Corporation Law of the
State of Delaware.

     7.   ADJUSTMENT FOR STOCK. All references to the number of Shares and the
purchase price of the Shares in this Agreement shall be appropriately adjusted
to reflect any stock split, stock dividend or other change in the Shares which
may be made by the Company after the date of this Agreement.

     8.   GENERAL 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 law.

          (b)    This Agreement and the documents referred to herein constitute
the entire agreement among the parties regarding the subject matters hereof and
thereof.

          (c)    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
the Company and Founder. Any amendment or waiver so effected shall be binding
upon the Founder, the Company and any assignee or successor of any such party.

          (d)    Any notices required in connection with this Agreement shall be
in writing and shall be deemed effectively given: (i) upon personal delivery to
the party to be notified, (ii) when sent by confirmed facsimile if sent during
normal business hours of the recipient, if not, then on the next business day,
(iii) five (5) days after having been sent by registered or certified mail,
return receipt requested, postage prepaid, or (iv) one (1) day after deposit
with a nationally recognized overnight courier, specifying next day delivery,
with written notification of receipt. All notices shall be addressed to the
applicable party to such party's address appearing on the signature page to this
Agreement or at such address as such party may designate by ten (10) days
advance written notice to the other parties hereto.

          (e)    All covenants and agreements hereunder shall inure to the
benefit of, and be enforceable by, the Company's successors and assigns. The
rights and obligations of the

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Founder under this Agreement may only be assigned with the prior written consent
of the Company.

          (f)    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.

          (g)    The Founder agrees upon request to execute any further
documents or instruments necessary or desirable to carry out the purposes or
intent of this Agreement.

          (h)    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.

          (i)    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.

          (j)    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.

          (k)    THE FOUNDER ACKNOWLEDGES AND AGREES THAT THE VESTING OF SHARES
PURSUANT TO SECTION 2 HEREOF IS EARNED ONLY BY CONTINUING SERVICE TO THE
COMPANY. THE FOUNDER FURTHER ACKNOWLEDGES AND AGREES THAT THIS AGREEMENT, THE
TRANSACTIONS CONTEMPLATED HEREUNDER AND THE VESTING SCHEDULE SET FORTH HEREIN DO
NOT CONSTITUTE AN EXPRESS OR IMPLIED PROMISE OF CONTINUED ENGAGEMENT AS AN
EMPLOYEE FOR THE VESTING PERIOD, FOR ANY PERIOD, OR AT ALL, AND SHALL NOT
INTERFERE WITH THE FOUNDERS RIGHT OR THE COMPANY'S RIGHT TO TERMINATE THE
FOUNDER'S EMPLOYMENT RELATIONSHIP AT ANY TIME, WITH OR WITHOUT CAUSE.

          (l)    The Founder has reviewed this Agreement in its entirety, has
had an opportunity to obtain the advice of counsel prior to executing this
Agreement and fully understands all provisions of the Agreement. The Founder
agrees to notify the Company upon any change in the residence address indicated
below.

                [Remainder of the page intentionally left blank.]

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

                                      COMPANY:

                                           COMBINATORX, INCORPORATED

                                           BY: /s/ Peter B. Finn
                                               ---------------------------------
                                               Name:
                                               Title:

                                           Address:      801 Albany Street
                                                         Suite G02
                                                         Boston, MA 02118

                                      FOUNDER:

                                           /s/ Alexis Borisy
                                           ---------------------------------
                                           Name: Alexis Borisy
                                           Address:

                                      ESCROW HOLDER:

                                           RUBIN AND RUDMAN LLP

                                           By: /s/ Peter B. Finn
                                               ---------------------------------
                                               Name:
                                               Title:
                                               Address:   50 Rowes Wharf
                                                          Boston, MA 02110-3319

                     [SIGNATURE PAGE TO FOUNDER'S AGREEMENT]

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                      ASSIGNMENT SEPARATE FROM CERTIFICATE

     FOR VALUE RECEIVED, ______________ hereby sells, assigns and transfers unto
________________ (__________) shares of the Common Stock of CombinatoRx,
Incorporated, a Delaware corporation (the "Company") standing in the name of
______________ on the books of said corporation represented by Certificate No.
______ herewith and do hereby irrevocably constitute and appoint Rubin and
Rudman LLP, attorney, to transfer the said stock on the books of the within
named corporation with full power of substitution in the premises.

     This Assignment Separate from Certificate may be used only in accordance
with the Founder's Agreement by and between the Company and the undersigned
dated January 26, 2001.

Dated: January 26, 2001

                                  Signature: /s/ Alexis Borisy
                                             --------------------------
                                             Name: Alexis Borisy

INSTRUCTION: PLEASE DO NOT FILL IN ANY BLANKS OTHER THAN THE SIGNATURE LINE. THE
PURPOSE OF THIS ASSIGNMENT IS TO ENABLE THE COMPANY TO EXERCISE ITS "REPURCHASE
OPTION" SET FORTH IN THE AGREEMENT WITHOUT REQUIRING ADDITIONAL SIGNATURES ON
THE PART OF THE FOUNDER.

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