Document:

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                                                                   EXHIBIT 10.15

January 23, 2006

Jason Cole, Esq.
40 Claflin Road, #3
Brookline, MA  02445

Dear Jason:

On behalf of CombinatoRx, Incorporated ("the Company"), I am pleased to offer
you the position of Senior Vice President and General Counsel. This position
will report to Alexis Borisy, President & CEO.

1. YOUR JOB RESPONSIBILITIES:

This position is the senior, in-house legal counsel and is responsible for
overseeing all legal matters pertaining to the organization including the SEC,
Business Development, Intellectual Property, Employment/Labor matters, and the
coordination of any legal subjects handled by outside counsel.

2. EFFECTIVE DATE: The effective date of your employment with the Company will
be on or about Monday, January 23, 2006. 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 subject to clause 5 below.

3. COMPENSATION: Your base pay will be $10,416.67 (equivalent to $250,000.00
annually), paid twice per month.

Further, in accordance with the Company's Stock Option Plan (the "Plan"), and
Incentive Stock Option Grant Agreement (the "Agreement"), you are hereby
eligible to be 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 at the fair market value. 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.

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 thirty (30%) percent of your then annual base compensation.

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, flexible spending account plan, life insurance, short term disability
insurance, and long term disability insurance. You will be eligible for a
Company-matched 401(k) plan upon employment. In addition to your compensation,
you will be entitled to three (3) weeks' vacation (in addition to our Winter
Holiday Week) 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
medical and dental benefits for a period of six (6) months from the date of
termination.

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JANUARY 2006
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The Company may terminate your employment, upon notice, for Cause, meaning that
there has been a reasonable, good faith determination that one or more of the
following events has occurred, which determination is made after notice to you
specifying in reasonable detail the nature of the Cause and a reasonable
opportunity for you to be heard. The following shall constitute Cause for
termination:

            (i)    Conviction of a felony;

            (ii)   Willful failure to perform (other than by reason of
     disability), or gross negligence in the performance of, your duties and
     responsibilities as set forth in your job description.

            (iii)  Material breach by you of any provision of this letter, which
     breach continues or remains uncured after thirty (30) days' notice setting
     forth in reasonable detail the nature of such breach; or

            (iv)   Material fraudulent conduct by you with respect to the
     Company.

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
your employment other than for Cause, then, the Company (A) shall provide you
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 your participation in the Company's group medical and dental
plans for a period of six (6) months following the date of termination, provided
that you are 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 you 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 you or for your 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"), you 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 your
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 and submit an
original document or documents that establish identity and employment
eligibility within three business days of employment. This 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

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JANUARY 2006
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separation from the Company, you agree to return to the Company all documents or
property, 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 to this Letter Agreement.

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

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

Sincerely,

/s/ Alexis Borisy

Alexis Borisy
President & CEO
CombinatoRx

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

   /s/ Jason Cole                             Date:    January 23, 2006
------------------------------------------         --------------------------
Jason Cole, Esq.<Page>

                                                                   Exhibit 10.30

                                                                  EXECUTION COPY

                      FIRST AMENDMENT TO RESEARCH AGREEMENT

     FIRST AMENDMENT TO RESEARCH AGREEMENT (this "AMENDMENT"), dated as of
December 15, 2005, by and between CombinatoRx, Incorporated, a Delaware
corporation (the "COMPANY"), and CHDI, Inc., a New Jersey corporation (the
"FOUNDATION"). The Company and the Foundation shall hereinafter be referred to
individually as a "PARTY" and collectively as the "PARTIES".

     WHEREAS, the Research Institution and the Foundation entered into that
certain Research Agreement, dated as of August 9, 2005 (such agreement as
amended shall hereinafter be referred to as the "AGREEMENT").

     WHEREAS, capitalized terms used herein but not otherwise defined shall have
the meanings ascribed thereto in the Agreement.

     WHEREAS, the parties hereto desire to amend, modify and supplement the
Agreement as provided herein.

     NOW THEREFORE, in consideration of the mutual representations, warranties
and covenants contained herein and other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the parties hereby
agree as follows:

1.   AMENDMENTS, MODIFICATIONS AND SUPPLEMENTS TO THE AGREEMENT.

     (a)  Section 3 of the Agreement is hereby amended by deleting such Section
          in its entirety and replacing it with the text attached hereto as
          EXHIBIT 1.

     (b)  Appendix C of the Agreement is hereby amended by deleting such
          appendix in its entirety and replacing it with the "Appendix C"
          attached hereto as EXHIBIT 2.

2.   SINGLE AGREEMENT; INCONSISTENT TERMS. This Amendment is hereby annexed to
     and forms a part of the Agreement. In the event of any inconsistency
     between the provisions of this Amendment and those contained in the
     Agreement to which this Amendment is annexed, the provisions of this
     Amendment shall govern and be binding.

3.   RATIFICATION OF THE AGREEMENT. The Agreement is hereby ratified by the
     parties hereto, and the terms and provisions of the Agreement as amended,
     modified and supplemented by this Amendment shall remain in full force and
     effect.

                                    * * * * *

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                                                                  EXECUTION COPY

     In witness to the foregoing, the Parties have executed this Amendment as of
the date first written above.

RESEARCH INSTITUTION:

CombinatoRx, Incorporated

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

FOUNDATION:

CHDI, Inc.

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

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                                                                  EXECUTION COPY

                                    EXHIBIT 1

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                                                                  EXECUTION COPY

3.   OBLIGATION TO MAKE PAYMENTS AND PAYMENT SCHEDULE; QUARTERLY FTE NOTICES;
     REVIEW OF QUARTERLY FTE NOTICE; CALCULATION OF ACTUAL QUARTERLY FTE COST;
     QUARTERLY PAYMENT ADJUSTMENT.

     (a)  OBLIGATION TO MAKE PAYMENTS AND PAYMENT SCHEDULE.

          (i)    OBLIGATION TO MAKE PAYMENTS. The Foundation shall make payments
                 to the Company for the Research Project as provided in, and
                 subject to the terms and conditions of, this Agreement. The
                 Company acknowledges and agrees that the Foundation shall not
                 be required to make any payment to the Company in respect of
                 any Phase of the Research Project for which each of the
                 Scientific Milestones has not been satisfied or achieved.

          (ii)   PAYMENT SCHEDULE. The amount of each quarterly payment (the
                 "QUARTERLY PAYMENTS") and milestone payment (the "MILESTONE
                 PAYMENTS" and, together with the Quarterly Payments, the
                 "PAYMENTS") are set forth on the payment schedule (the "PAYMENT
                 SCHEDULE") attached hereto as APPENDIX D.

     (b)  QUARTERLY FTE NOTICES.

          (i)    DELIVERY OF THE QUARTERLY FTE NOTICES. The Company shall
                 deliver a written notice (each, a "QUARTERLY FTE NOTICE") to
                 the Foundation promptly following the end of each 90-day period
                 (each, a "QUARTERLY FTE NOTICE PERIOD") during the period
                 beginning on the Effective Date and continuing through the
                 Quarterly FTE Notice Period following the last scheduled
                 Quarterly Payment made by the Foundation under the terms of
                 this Agreement.

          (ii)   REQUIRED INFORMATION IN EACH QUARTERLY FTE NOTICE. Each
                 Quarterly FTE Notice shall be given in respect of the most
                 recently ended Quarterly FTE Notice Period (the "CURRENT NOTICE
                 PERIOD") and shall:

                 (A)  set forth the Quarterly Payment number and the year and
                      quarter of the Research Project (in each case, as set
                      forth in APPENDIX D) covered by the Current Notice Period;

                 (B)  identify each Phase of the Research Project (each, an
                      "APPROVED ACTIVE PHASE") for which each of the Scientific
                      Milestones required to proceed to conduct or perform such
                      Phase of the Research Project has been satisfied or
                      achieved;

                 (C)  with respect to each Approved Active Phase, set forth the
                      number of FTEs budgeted to devote time to such Approved

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                      Active Phase during the Current Notice Period as set forth
                      in APPENDIX B (the "CURRENT NOTICE PERIOD BUDGETED FTEs");

                 (D)  with respect to each Approved Active Phase, set forth (1)
                      the name and title of each individual who actually devoted
                      time to such Approved Active Phase during the Current
                      Notice Period and (2) the number of FTEs that actually
                      devoted time to such Approved Active Phase during the
                      Current Notice Period (the "CURRENT NOTICE PERIOD ACTUAL
                      FTEs") (such amount to be calculated by dividing the
                      number of weeks (or pro rata portion thereof) such
                      individual actually devoted one-hundred percent of his or
                      her effort to such Approved Active Phase during the
                      Current Notice Period by the number 13);

                 (E)  with respect to each Approved Active Phase, set forth the
                      positive difference, if any, between (1) the aggregate
                      number of FTEs budgeted to devote time to such Approved
                      Active Phase during all previous Quarterly FTE Notice
                      Periods as set forth in APPENDIX B MINUS (2) the aggregate
                      number of FTEs that actually devoted one-hundred percent
                      of such aggregate FTE's effort to such Approved Active
                      Phase as set forth in all prior Quarterly FTE Notices
                      delivered by the Company and approved by the Foundation in
                      accordance with this SECTION 3 (such difference
                      hereinafter referred to as the "CURRENT NOTICE PERIOD
                      CARRYOVER BUDGETED FTEs BEGINNING BALANCE");

                 (F)  with respect to each Approved Active Phase, set forth the
                      sum of (1) the Current Notice Period Budgeted FTEs PLUS
                      (2) the Current Notice Period Carryover Budgeted FTEs
                      Beginning Balance (such sun hereinafter referred to as the
                      "CURRENT NOTICE PERIOD TOTAL AVAILABLE BUDGETED FTEs");

                 (G)  with respect to each Approved Active Phase, set forth the
                      positive difference, if any, between (1) the Current
                      Notice Period Total Available Budgeted FTEs MINUS (2) the
                      Current Notice Period Actual FTEs (such difference
                      hereinafter referred to as the "CURRENT NOTICE PERIOD
                      CARRYOVER BUDGETED FTEs ENDING BALANCE");

                 (H)  include a certification by the Company that all of the
                      information provided in such Quarterly FTE Notice is true,
                      complete and correct.

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     (c)  REVIEW OF QUARTERLY FTE NOTICE; ACTUAL QUARTERLY FTE COST; QUARTERLY
          PAYMENT ADJUSTMENT.

          (i)    REVIEW OF QUARTERLY FTE NOTICE. Beginning on the date of the
                 receipt of a Quarterly FTE Notice in respect of a Current
                 Notice Period, the Foundation shall have a period (the
                 "QUARTERLY PAYMENT ADJUSTMENT REVIEW PERIOD") of 20 days to (A)
                 review such Quarterly FTE Notice and (B) request such
                 additional information from the Company as may be reasonably
                 required by the Foundation to verify the information set forth
                 in such Quarterly FTE Notice.

          (ii)   ACTUAL QUARTERLY FTE COST. Within 10 days of the expiration of
                 the Quarterly Payment Adjustment Review Period, the Foundation
                 shall calculate the cost (the "ACTUAL QUARTERLY FTE COST") of
                 (A) the budgeted management FTE set forth in APPENDIX B for
                 such Current Notice Period and (B) the Current Notice Period
                 Actual FTEs for each Approved Active Phase for such Current
                 Notice Period; provided, however, the amount of Current Notice
                 Period Actual FTEs used in any such calculation shall not
                 exceed the Current Notice Period Total Available Budgeted FTEs
                 for each Approved Active Phase for such Current Notice Period.
                 For purposes of this Agreement, all calculations shall be made
                 using a FTE rate of $250,000 per year other than FTEs allocated
                 to Phase 2 for which a FTE rate of $275,000 shall be used.

          (iii)  QUARTERLY PAYMENT ADJUSTMENT.

                 (A)  QUARTERLY PAYMENT CREDIT AMOUNT; AGGREGATE QUARTERLY
                      PAYMENT HOLDBACK AMOUNT. If the Actual Quarterly FTE Cost
                      for such Current Notice Period is less than the Quarterly
                      Payment made by the Foundation in respect of such Current
                      Notice Period, either (1) the Foundation shall credit an
                      amount (each, a "CURRENT NOTICE PERIOD QUARTERLY PAYMENT
                      CREDIT AMOUNT") equal to the difference between the
                      Quarterly Payment made by the Foundation in respect of
                      such Current Notice Period MINUS the Actual Quarterly FTE
                      Cost for such Current Notice Period against any future
                      payments required to be made by the Foundation to the
                      Company under this Agreement or (2) upon the written
                      request of the Foundation, the Company shall pay an amount
                      (each, a "CURRENT NOTICE PERIOD QUARTERLY PAYMENT REFUND
                      AMOUNT") equal to the difference between the Quarterly
                      Payment made by the Foundation in respect of such Current
                      Notice Period MINUS the Actual Quarterly FTE Cost for such
                      Current Notice Period to the Foundation within 30 days of
                      the receipt of any such written request.

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                      For purposes of this Agreement, the aggregate of all
                      Current Notice Period Quarterly Payment Credit Amounts and
                      Current Notice Period Quarterly Payment Refund Amounts
                      LESS the aggregate of all Quarterly Payment Increase
                      Amounts (as defined in SECTION 3(c)(iii)(B) of this
                      Agreement) paid by the Foundation to the Company pursuant
                      to SECTION 3(c)(iii)(B) of this Agreement shall be
                      referred to as the "AGGREGATE QUARTERLY PAYMENT HOLDBACK
                      AMOUNT".

                 (B)  QUARTERLY PAYMENT INCREASE AMOUNT. If (1) the Actual
                      Quarterly FTE Cost for such Current Notice Period is
                      greater than the Quarterly Payment made by the Foundation
                      in respect of such Current Notice Period and (2) the
                      Aggregate Quarterly Payment Holdback Amount is greater
                      than zero, the Foundation shall increase the amount of the
                      next scheduled Quarterly Payment by an amount (each, a
                      "QUARTERLY PAYMENT INCREASE AMOUNT") equal to the lesser
                      of (a) the difference between the Actual Quarterly FTE
                      Cost for such Current Notice Period MINUS the Quarterly
                      Payment made by the Foundation in respect of such Current
                      Notice Period and (b) the then outstanding Aggregate
                      Quarterly Payment Holdback Amount.

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                                                                  EXECUTION COPY

                                    EXHIBIT 2

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                                                                  EXECUTION COPY

                        APPENDIX C TO RESEARCH AGREEMENT

                             (SCIENTIFIC MILESTONES)

RESEARCH PROJECT - SCIENTIFIC MILESTONES

<Table>
<Caption>
RESEARCH PROJECT PHASE                                        CONDITION(S) TO BEGIN CONDUCT OF PHASE
------------------------------------------------- ---------------------------------------------------------------
<S>                                               <C>
Phase 1 through Phase 5                           Execution of this Agreement by the Parties.

                                                  The Research Committee has made each decision and granted each
                                                  approval expressly set forth in this Agreement that is
                                                  specifically required or otherwise necessary to begin the
                                                  conduct of any specific Phase of the Research Project.

Phase 1A                                          Execution of this Agreement by the Parties.

Phase 1B - Part 1                                 Execution of this Agreement by the Parties.

Phase 1B - Part 2                                 The Research Committee has approved at least one cell line for
                                                  use as the parental cell line for the generation of the TRex
                                                  Flp-In neuroblastoma cell line by Invitrogen within six months
                                                  of the Effective Date.

                                                  The Foundation and Invitrogen have executed the Invitrogen
                                                  Agreement within six months of the Effective Date.

                                                  Invitrogen has delivered the TRex Flp-In neuroblastoma cell
Phase 1B - Part 3                                 line to the Company within 12 months of the execution of the
                                                  Invitrogen Agreement.

Phase 1C                                          Execution of this Agreement by the Parties.

Phase 2 and 3 - Use of Assay 1 for Screening      Complete optimization of Assay 1 within four months following
                                                  the date the Company has taken delivery of the cell line
                                                  approved by the Research Committee for use in the optimization
                                                  of Assay 1.

                                                  Assay 1 meets each of the specifications set forth in
                                                  APPENDIX A and is approved by the Research Committee for use in
                                                  Phase 2 and 3.

Phase 2 and 3 - Use of Assay 2 for Screening      Complete development and optimization of Assay 2 within five
                                                  months following the delivery of the TRex Flp-In
                                                  neuroblastoma cell line to the Company.

                                                  Assay 2 meets each of the specifications set forth in
                                                  APPENDIX A and is approved by the Research Committee for use in
                                                  Phase 2 and 3.
</Table>

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<Table>
<S>                                               <C>
Phase 2 and 3 - Use of Assay 3 for Screening      Complete development and optimization of Assay 3 within nine
                                                  months following the date cell lines and htt specific
                                                  antibodies approved by the Research Committee for use in the
                                                  development and optimization of Assay 3 are acquired by, or
                                                  on behalf of, the Company.

                                                  Assay 3 meets each of the specifications set forth in
                                                  APPENDIX A and is approved by the Research Committee for use in
                                                  Phase 2 and 3.

Phase 2A                                          The Company has (a) selected at least 1,300 Company
                                                  Library Compounds within one month of the approval by the
                                                  Research Committee of any of the Assays for use in Phase 2
                                                  and 3 and (b) acquired each Foundation Selected Compound
                                                  within one month of the selection of such compounds by the
                                                  Foundation.

Phase 2B                                          The screening required by Phase 2A has been completed within 26
                                                  months of the Effective Date.

                                                  The combination screening strategy for Phase 2B is approved by the
                                                  Research Committee.

Phase 3                                           The Research Committee approves at least one Phase 3
                                                  Approved Compound Combination.

Phase 4                                           The Research Committee approves at least one Phase 4
                                                  Approved Compound Combination.

Phase 5                                           The Foundation approves at least one Phase 5 Approved
                                                  Compound Combination.
</Table>

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