<PAGE>

                                                                   EXHIBIT 10.49

                         EXECUTIVE EMPLOYMENT AGREEMENT

      EMPLOYMENT AGREEMENT (the "Agreement") made as of June 8, 2000 between
ARIAD Pharmaceuticals, Inc. (the "Company") a Delaware corporation, and Timothy
Clackson, Ph.D. (the "Employee").

      1.    Employment, Duties and Acceptance.

            1.1   The Company hereby employs the Employee, for the Term (as
hereinafter defined), to render full-time services to the Company, and to
perform such duties as he shall reasonably be directed by the Chief Executive
Officer of the Company to perform. The Employee's title shall be designated by
the Chief Executive Officer and initially shall be Vice President, Gene Therapy.

            1.2   The Employee hereby accepts such employment and agrees to
render the services described above.

            1.3   The principal place of employment of the Employee hereunder
shall be in the greater Boston, Massachusetts area, or other locations
reasonably acceptable to the Employee. The Employee acknowledges that for
limited periods of time he may be required to provide services to the Company
outside of the Boston, Massachusetts area.

            1.4   Notwithstanding anything to the contrary herein, although the
Employee shall provide services as a full-time employee, it is understood that
the Employee may (a) have an academic appointment and (b) participate in
professional activities (collectively, "Permitted Activities'); provided,
however, that such Permitted Activities do not interfere with the Employee's
duties to the Company.


                                       1
<PAGE>
      2.    Term of Employment.

            The term of the Employee's employment under this Agreement (the
"Term") shall commence July 1, 2000 (the "Effective Date") and shall end on
December 31, 2001 unless sooner terminated pursuant to Section 4 or 5 of this
Agreement; provided that this Agreement shall automatically be renewed for
successive one-year terms (the Term and, if the period of employment is so
renewed, such additional period(s) of employment are collectively referred to
herein as the "Term") unless terminated by written notice given by either party
to the other at least ninety days prior to the end of the applicable Term.

      3.    Compensation.

            3.1   As full compensation for all services to be rendered pursuant
to this Agreement, the Company agrees to pay the Employee, during the Term, a
salary at the fixed rate of $135,000 per annum during the first year of the Term
and increased each year thereafter, by amounts, if any, to be determined by the
Board of Directors of the Company (the "Board"), in its sole discretion, payable
in equal biweekly installments, less such deductions or amounts to be withheld
as shall be required by applicable law and regulations.

            3.2   Each year, the Company shall pay the Employee a discretionary
bonus of up to 30% of base salary, which bonus shall be determined annually by
the Board. The bonus, if any, may be paid in the form of stock options, stock
awards, deferred compensation or cash, as determined by the Board.

            3.3   The Company shall pay or reimburse the Employee for all
reasonable expenses actually incurred or paid by him during the Term in the
performance of his services under this Agreement,


                                       2
<PAGE>
upon presentation of expense statements or vouchers or such other supporting
information as it may require.

            3.4   The Employee shall be eligible under any incentive plan, stock
award plan, bonus, participation or extra compensation plan, pension, group
health, disability and life insurance or other so-called "fringe" benefits which
the Company provides for its executives at the comparable level. All options and
stock awards granted to the Employee shall be subject to a vesting schedule
which shall be determined by the Compensation and Stock Option Committee of the
Board. The options and awards, if any, to be granted to the Employee shall also
be subject to the terms of a stock option plan and certificate and stock award
plan and certificate, respectively. Any unvested options shall be forfeited to
the Company in the event (a) this Agreement is terminated by the Company for
Cause pursuant to Section 4 herein, or (b) either party elects not to renew this
Agreement pursuant to Section 2 herein.

      4.    Termination by the Company.

            The Company may terminate this Agreement, if any one or more of the
following shall occur:

                  (a)   The Employee shall die during the Term; provided,
however, the Employee's legal representatives shall be entitled to receive the
compensation provided for hereunder to the last day of the month in which his
death occurs.

                  (b)   The Employee shall become physically or mentally
disabled, whether totally or partially, so that he is unable substantially to
perform his services hereunder for (i) a period of 180 consecutive days, or (ii)
for shorter periods aggregating 180 days during any twelve month period.


                                       3
<PAGE>
                  (c)   The Employee acts, or fails to act, in a manner that
provides Cause for termination. For purposes of this Agreement, the term "Cause"
means (i) the failure by the Employee to perform any of his material duties
hereunder, (ii) the conviction of the Employee of any felony involving moral
turpitude, (iii) any acts of fraud or embezzlement by the Employee involving the
Company or any of its Affiliates, (iv) violation of any federal, state or local
law, or administrative regulation related to the business of the Company, (v) a
conflict of interest, (vi) conduct that could result in publicity reflecting
unfavorably on the Company in a material way, (vii) failure to comply with the
written policies of the Company, or (viii) a breach of the terms of this
Agreement by the Employee. The Company shall provide the Employee written notice
of termination pursuant to this Section 4, and Employee shall have 30 days to
cure or remedy such failure or breach, in which case this Agreement shall not be
terminated.

      5.    Termination by the Employee.

            5.1   The Employee may terminate this Agreement, if any one or more
of the following shall occur:

                  (a)   a material breach of the terms of this Agreement by the
Company and such breach continues for 30 days after the Employee gives the
Company written notice of such breach;

                  (b)   the Company shall make a general assignment for benefit
of creditors; or any proceeding shall be instituted by the Company seeking to
adjudicate it as bankrupt or insolvent, or seeking liquidation, winding up,
reorganization, arrangement, adjustment, protection, relief, or composition of
it or its debts under law


                                       4
<PAGE>
relating to bankruptcy, insolvency or reorganization or relief of debtors, or
seeking entry of an order for relief or the appointment of a receiver, trustee,
or other similar official for it or for any substantial part of its property or
the Company shall take any corporate action to authorize any of the actions set
forth above in this subsection 5(b);

                  (c)   an involuntary petition shall be filed or an action or
proceeding otherwise commenced against the Company seeking reorganization,
arrangement or readjustment of the Company's debts or for any other relief under
the Federal Bankruptcy Code, as amended, or under any other bankruptcy or
insolvency act or law, state or federal, now or hereafter existing and remain
undismissed or unstayed for a period of 30 days; or

                  (d)   a receiver, assignee, liquidator, trustee or similar
officer for the Company or for all or any part of its property shall be
appointed involuntarily.

      6.    Severance.

            If (i) the Company terminates this Agreement without Cause or (ii)
the Employee terminates this Agreement pursuant to Section 5.1(a), then: (1)
except in the case of death or disability, the Company shall continue to pay
Employee his current salary for the remaining period of the applicable Term; (2)
all options granted to the Employee that would have vested during the Term shall
vest immediately prior to such termination; and (3) the Company shall continue
to provide all benefits subject to COBRA at its expense for up to one year.

      7.    Other Benefits.

            In addition to all other benefits contained herein, the Employee
shall be entitled to:


                                       5
<PAGE>
                  (a)   Vacation time of four weeks per year taken in accordance
with the vacation policy of the Company.

                  (b)   After six years of employment, one three-month period of
fully paid leave of absence in accordance with Company policies in place at that
time; it being understood that such policies may restrict the Employee from
taking such leave of absence until a time that is acceptable to the Company and
may include other such limitations.

                  (c)   Group health, disability and life insurance.

                  (d)   The Company shall provide the Employee with an
automobile allowance of $750 per month.

      8.    Confidentiality.

            8.1   The Employee acknowledges that, during the course of
performing his services hereunder, the Company shall be disclosing information
to the Employee related to the Company's Field of Interest, Inventions, projects
and business plans, as well as other information (collectively, "Confidential
Information"). The Employee acknowledges that the Company's business is
extremely competitive, dependent in part upon the maintenance of secrecy, and
that any disclosure of the Confidential Information would result in serious harm
to the Company.

            8.2   The Employee agrees that the Confidential Information only
shall be used by the Employee in connection with his activities hereunder as an
employee of the Company, and shall not be used in any way that is detrimental to
the Company.

            8.3   The Employee agrees not to disclose, directly or indirectly,
the Confidential Information to any third person or entity, other than
representatives or agents of the Company. The Employee shall


                                       6
<PAGE>
treat all such information as confidential and proprietary property of the
Company.

            8.4   The term "Confidential Information" does not include
information that (a) is or becomes generally available to the public other than
by disclosure in violation of this Agreement, (b) was within the Employee's
possession prior to being furnished to such Employee, (c) becomes available to
the Employee on a nonconfidential basis or (d) was independently developed by
the Employee without reference to the information provided by the Company.

            8.5   The Employee may disclose any Confidential Information that is
required to be disclosed by law, government regulation or court order. If
disclosure is required, the Employee shall give the Company advance notice so
that the Company may seek a protective order or take other action reasonable in
light of the circumstances.


            8.6   Upon termination of this Agreement, the Employee
shall promptly return to the Company all materials containing Confidential
Information, as well as data, records, reports and other property, furnished by
the Company to the Employee or produced by the Employee in connection with
services rendered hereunder. Notwithstanding such return or any of the
provisions of this Agreement, the Employee shall continue to be bound by the
terms of the confidentiality provisions contained in this Section 8 for a period
of three years after the termination of this Agreement.

            8.7   In connection with his employment by the Company, the Employee
hereby acknowledges that he may enter into more than one agreement with regard
to (a) the confidentiality of certain


                                       7
<PAGE>
books, records, documents and business, (b) rights to certain inventions,
proprietary information, and writings, (c) publication of certain materials, and
(d) other related matters (the "Confidential Matters") of the Company (the
"Confidentiality Agreements"). In order to clarify any potential conflicts
between certain respective provisions of such Confidentiality Agreements, the
Employee and the Company hereby agree that, as among such Confidentiality
Agreements, the provision (or part thereof) in any such Confidentiality
Agreement which affords the greatest protection to the Company with respect to
the Confidential Matters shall control.

      9.    Inventions Discovered by the Employee While Performing Services
Hereunder.

            During the Term, the Employee shall promptly disclose to the Company
any invention, improvement, discovery, process, formula, or method or other
intellectual property, whether or not patentable, whether or not copyrightable
(collectively, "Inventions") made, conceived or first reduced to practice by the
Employee, either alone or jointly with others, while performing service
hereunder. The Employee hereby assigns to the Company all of his right, title
and interest in and to any such Inventions. During and after the Term, the
Employee shall execute any documents necessary to perfect the assignment of such
Inventions to the Company and to enable the Company to apply for, obtain, and
enforce patents and copyrights in any and all countries on such Inventions. The
Employee hereby irrevocably designates the Chief Patent Counsel to the Company
as his agent and attorney-in-fact to execute and file any such document and to
do all lawful acts necessary to apply for and obtain patents and copyrights and
to enforce the Company's


                                       8
<PAGE>
rights under this paragraph. This Section 9 shall survive the termination of
this Agreement.

      10.   Non-Competition and Non-Solicitation.

            During the Term and for a period of one year following the date of
termination or nonrenewal for any reason (other than termination pursuant to
Section 5.1(a): (a) the Employee shall not in the United States or in any
country in which the Company shall then be doing business, directly or
indirectly, enter the employ of, or render any services to, any person, firm or
corporation engaged in any business competitive with the business of the Company
or of any of its subsidiaries or affiliates of which the Employee may become an
employee or officer during the Term; he shall not engage in such business on his
own account; and he shall not become interested in any such business, directly
or indirectly, as an individual, partner, shareholder, director, officer,
principal, agent, employee, trustee, consultant, or any other relationship or
capacity; provided, however, that nothing contained in this Section 10 shall be
deemed to prohibit the Employee from acquiring, solely as an investment, shares
of capital stock of any public corporation; (b) neither the Employee nor any
Affiliate of the Employee shall solicit or utilize, or assist any person in any
way to solicit or utilize, the services, directly or indirectly, of any of the
Company's directors, consultants, members of the Board of Scientific and Medical
Advisors, officers or employees (collectively, "Associates of the Company").
This nonsolicitation and nonutilization provision shall not apply to Associates
of the Company who have previously terminated their relationship with the
Company.


                                       9
<PAGE>
            10.1  If the Employee commits a breach, or threatens to commit a
breach, of any of the provisions of this Section 10, the Company shall have the
following rights and remedies:

                  10.1.1 The right and remedy to have the provisions of this
Agreement specifically enforced by any court having equity jurisdiction, it
being acknowledged and agreed that any such breach or threatened breach shall
cause irreparable injury to the Company and that money damages shall not provide
an adequate remedy to the Company; and

                  10.1.2 The right and remedy to require the Employee to account
for and pay over to the Company all compensation, profits, monies, accruals,
increments or other benefits (collectively "Benefits") derived or received by
the Employee as the result of any transactions constituting a breach of any of
the provisions of the preceding paragraph, and the Employee hereby agrees to
account for and pay over such Benefits to the Company. Each of the rights and
remedies enumerated above shall be independent of the other, and shall be
severally enforceable, and all of such rights and remedies shall be in addition
to, and not in lieu of, any other rights and remedies available to the Company
under law or in equity.

            10.2  If any of the covenants contained in Section 8, 9 or 10, or
any part thereof, is hereafter construed to be invalid or unenforceable, the
same shall not affect the remainder of the covenant or covenants, which shall be
given full effect without regard to the invalid portions.

            10.3  If any of the covenants contained in Section 8, 9 or 10, or
any part thereof, is held to be unenforceable because of the


                                       10
<PAGE>
duration of such provision or the area covered thereby, the parties agree that
the court making such determination shall have the power to reduce the duration
and/or area of such provision and, in its reduced form, such provision shall
then be enforceable.

            10.4  The parties hereto intend to and hereby confer jurisdiction to
enforce the covenants contained in Sections 8, 9 and 10 upon the courts of any
state within the geographical scope of such covenants. In the event that the
courts of any one or more of such states shall hold any such covenant wholly
unenforceable by reason of the breadth of such scope or otherwise, it is the
intention of the parties hereto that such determination not bar or in any way
affect the Company's right to the relief provided above in the courts of any
other states within the geographical scope of such covenants, as to breaches of
such covenants in such other respective jurisdictions, the above covenants as
they relate to each state being, for this purpose, severable into diverse and
independent covenants.

      11.   Indemnification.

            The Company shall indemnify the Employee, to the maximum extent
permitted by applicable law, against all costs, charges and expenses incurred or
sustained by him in connection with any action, suit or proceeding to which he
may be made a party by reason of his being an officer, director or employee of
the Company or of any subsidiary or affiliate of the Company. The Company shall
provide, subject to its availability upon reasonable terms (which determination
shall be made by the Board) at its expense, directors and officers insurance for
the Employee in reasonable amounts. Determination with respect to (a) the


                                       11
<PAGE>
availability of insurance upon reasonable terms and (b) the amount of such
insurance coverage shall be made by the Board in its sole discretion.

      12.   Notices.

            All notices, requests, consents and other communications required or
permitted to be given hereunder shall be in writing and shall be deemed to have
been duly given if sent by prepaid telegram (confirmed delivery by the telegram
service), private overnight mail service (delivery confirmed by such service),
registered or certified mail (return receipt requested), or delivered
personally, as follows (or to such other address as either party shall designate
by notice in writing to the other in accordance herewith):

      If to the Company:

      ARIAD Pharmaceuticals, Inc.
      26 Landsdowne Street
      Cambridge, Massachusetts 02139
      Attention: Chief Executive Officer
      Telephone:  (617) 494-0400
      Fax:        (617) 494-1828


      If to the Employee:

      Timothy Clackson, Ph.D.
      21 Kensington Park
      Arlington, Massachusetts  02476


      13.   General.

            13.1  This Agreement shall be governed by and construed and enforced
in accordance with the laws of the Commonwealth of Massachusetts applicable to
agreements made and to be performed entirely in Massachusetts.


                                       12
<PAGE>
            13.2  The Section headings contained herein are for reference
purposes only and shall not in any way affect the meaning or interpretation of
this Agreement.

            13.3  This Agreement sets forth the entire agreement and
understanding of the parties relating to the subject matter hereof, and
supersedes all prior agreements, arrangements and understandings, written or
oral, relating to the subject matter hereof. No representation, promise or
inducement has been made by either party that is not embodied in this Agreement,
and neither party shall be bound by or liable for any alleged representation,
promise or inducement not so set forth.

            13.4  This Agreement and the Employee's rights and obligations
hereunder may not be assigned by the Employee or the Company; provided, however,
the Company may assign this Agreement to an Affiliate or a successor-in
interest.

            13.5  This Agreement may be amended, modified, superseded, canceled,
renewed or extended, and the terms or covenants hereof may be waived, only by a
written instrument executed by the parties hereto, or in the case of a waiver,
by the party waiving compliance. The failure of a party at any time or times to
require performance of any provision hereof shall in no manner affect the right
at a later time to enforce the same. No waiver by a party of the breach of any
term or covenant contained in this Agreement, whether by conduct or otherwise,
in any one or more instances, shall be deemed to be, or construed as, a further
or continuing waiver of any such breach, or a waiver of the breach of any other
term or covenant contained in this Agreement.


                                       13
<PAGE>
      14.   Definitions. As used herein the following terms have the following
meaning:

            (a)   "Affiliate" means and includes any corporation or other
business entity controlling, controlled by or under common control with the
corporation in question.

            (b)   The "Company's Field of Interest" is the discovery,
development and commercialization of pharmaceutical products based on (a)
intervention in signal transduction pathways and (b) gene and cell therapy. The
Company's Field of Interest may be changed at any time at the sole discretion of
the Company.

            (c)   "person" means any natural person, corporation, partnership,
firm, joint venture, association, joint stock company, trust, unincorporated
organization, governmental body or other entity.

            (d)   "Subsidiary" means any corporation or other business entity
directly or indirectly controlled by the corporation in question.

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




                              ARIAD PHARMACEUTICALS, INC.


                              By       /s/ Harvey J. Berger
                                ------------------------------------------
                                Harvey J. Berger, M.D.
                                Chairman and Chief Executive Officer



                                       14
<PAGE>
                              EMPLOYEE


                                       /s/ Timothy Clackson
                              --------------------------------------------
                              Timothy Clackson, Ph.D.



                                       15