Document:

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                                                                    Exhibit 10.8

                              TERMINATION AGREEMENT

      THIS TERMINATION AGREEMENT (this "Agreement") is made and entered into
this ___ day of _____ by and between Texas Biotechnology Corporation, a Delaware
corporation with its principal office at 7000 Fannin, Houston, Texas 77030 (the
"Company"), and ______________ (the "Executive").

                                 R E C I T A L S

      A. The Company desires to enter into an agreement with the Executive
whereby severance benefits will be paid to the Executive on a change in control
of the Company and consequent actual or constructive termination of the
Executive's employment.

      B. This Agreement sets forth the severance benefits that the Company
agrees that it will pay to the Executive if the Executive's employment with the
Company terminates under one of the circumstances described herein following a
change in control of the Company.

      NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants contained herein, the parties hereto agree as follows:

      1. Term of Agreement. This Agreement shall be effective immediately on the
date hereof and shall continue in effect through _____; provided, however, that
commencing on _____ and each _____ thereafter, the term of this Agreement shall
automatically be extended for one additional year unless not later than _____ of
the preceding year, the Company shall have given notice that it does not wish to
extend this Agreement; provided, further, that notwithstanding any such notice
by the Company not to extend, this Agreement shall automatically be extended for
24 months beyond the term provided herein if a Change in Control (as defined in
Section 3 hereof) has occurred during the term of this Agreement.

      2. Effect on Employment Rights. This Agreement is not part of any
employment agreement that the Company and the Executive may have entered.
Nothing in this Agreement shall confer upon the Executive any right to continue
in the employ of the Company or interfere with or restrict in any way the rights
of the Company, which are hereby expressly reserved, to terminate the Executive
for any reason, with or without cause.

      The Executive agrees that, subject to the terms and conditions of this
Agreement, in the event of a potential Change in Control of the Company (as
defined below), the Executive will remain in the employ of the Company during
the pendency of any such potential Change in Control and for a period of one
year after the occurrence of an actual Change in Control. For this purpose, a
"potential Change in Control of the Company" shall be deemed to have occurred if
(a) the Company enters into an agreement the consummation of which would result
in the occurrence of a Change in Control, (b) any person (including the Company)
publicly announces an intention to take or consider taking action which if
consummated would constitute a Change
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in Control or (c) the Board of Directors of the Company (the "Board") adopts a
resolution to the effect that a potential Change in Control of the Company has
occurred.

      3. Change in Control. For purposes of this Agreement, a "Change in
Control" of the Company shall be deemed to have occurred if any of the events
set forth in any one of the following paragraphs shall occur:

            (a) any "person" (as defined in section 3(a)(9) of the Securities
      Exchange Act of 1934, as amended (the "Exchange Act"), and as such term is
      modified in sections 13(d) and 14(d) of the Exchange Act), excluding the
      Company or any of its subsidiaries, a trustee or any fiduciary holding
      securities under an employee benefit plan of the Company of any of its
      subsidiaries, an underwriter temporarily holding securities pursuant to an
      offering of such securities or a corporation owned, directly or
      indirectly, by stockholders of the Company in substantially the same
      proportions as their ownership of the Company, is or becomes the
      "beneficial owner" (as defined in Rule 13d-3 under the Exchange Act),
      directly or indirectly, of securities of the Company representing 30% or
      more of the combined voting power of the Company's then outstanding
      securities; or

            (b) during any period of not more than two consecutive years,
      individuals who at the beginning of such period constitute the Board and
      any new director (other than a director designated by a Person who has
      entered into an agreement with the Company to effect a transaction
      described in clause (a), (c) or (d) of this Section 3) whose election by
      the Board or nomination for election by the Company's stockholders was
      approved by a vote of at least two-thirds (2/3) of the directors then
      still in office who either were directors at the beginning of the period
      or whose election or nomination for election was previously so approved,
      cease for any reason to constitute a majority thereof; or

            (c) the stockholders of the Company approve a merger or
      consolidation of the Company with any other corporation, other than (i) a
      merger or consolidation which would result in the voting securities of the
      Company outstanding immediately prior thereto continuing to represent
      (either by remaining outstanding or by being converted into voting
      securities of the surviving entity), in combination with the ownership of
      any trustee or other fiduciary holder of securities under an employee
      benefit plan of the Company, at least 50% of the combined voting power of
      the voting securities of the Company or such surviving entity outstanding
      immediately after such merger or consolidation, or (ii) a merger or
      consolidation effected to implement a recapitalization of the Company (or
      similar transaction) in which no person acquires more than 50% of the
      combined voting power of the Company's then outstanding securities; or

            (d) the stockholders of the Company approve a plan of complete
      liquidation of the Company or an agreement for the sale or disposition by
      the Company of all or substantially all of the Company's assets.

      Notwithstanding the foregoing, no Change in Control shall be deemed to
      have occurred if there is consummated any transaction or series of
      integrated transactions immediately following which, in the judgment of
      the Compensation Committee of the Board, the holders of the Company's
      common stock, par value $.05 per share (the "Common Stock"), immediately
      prior to such transaction or series of transactions continue to have

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      the same proportionate ownership in an entity which owns all or
      substantially all of the assets of the Company immediately prior to such
      transaction or series of transactions. Except during a potential Change in
      Control of the Company, the Board may (i) deem any other corporate event
      affecting the Company (other than those described in clauses (a)-(d) of
      Section 3 above) to be a "Change in Control," and (ii) may amend this
      provision and the definition of "Change in Control" in connection with an
      identical amendment being made to the Termination Agreements entered into
      by the Company and certain of its executives.

      4. Termination of Employment Following a Change in Control. The Executive
shall be entitled to the benefits provided in Section 5 hereof upon the
subsequent termination of the Executive's employment by the Company within two
years after a Change in Control which occurs during the term of this Agreement,
provided such termination is (a) by the Company other than for Cause (as defined
below) or (b) by the Executive for Good Reason (as defined below). The Executive
shall not be entitled to the benefits of Section 5 hereof, any other provision
hereof to the contrary notwithstanding, if the Executive's employment
terminates: (i) pursuant to the Executive retiring at age 65, (ii) by reason of
the Executive's total and permanent disability (as defined below), or (iii) by
reason of the Executive's death. As used herein, "total and permanent
disability" means an illness or other disability that prevents the Executive
from discharging his responsibilities for a period of 180 consecutive calendar
days, or an aggregate of 180 calendar days in any calendar year, during his
employment with the Company, all as determined in good faith by the Board (or a
committee thereof).

            (a) Cause. The Company may terminate the Executive's employment with
      the Company, upon written notice to the Executive delivered in accordance
      with Sections 4(c) and 12 hereof, for Cause. For purposes of this
      definition of "Cause," the term "Company" shall mean the Company and/or
      its Affiliates. For purposes of this Agreement, subject to the notice
      provisions set forth below, "Cause" means (i) the conviction (or plea of
      nolo contendere or equivalent plea) of the Executive of a felony (which,
      through lapse of time or otherwise, is not subject to appeal), (ii) the
      Executive having engaged in intentional misconduct causing a violation by
      the Company of any state or federal laws which results in a material
      injury to the business, condition (financial or otherwise), results of
      operations or prospects of the Company as determined in good faith by the
      Board or a committee thereof (a "Material Injury"), (iii) the Executive
      having engaged in a theft of corporate funds or corporate assets of the
      Company or in an act of fraud upon the Company, (iv) an act of personal
      dishonesty taken by the Executive that was intended to result in personal
      enrichment of the Executive at the expense of the Company, (v) the
      Executive's refusal, without proper legal cause, to perform his duties and
      responsibilities as contemplated in this Agreement or any other breach by
      the Executive of this Agreement, and (vi) the Executive's engaging in
      activities which would constitute a breach of the Company's business
      ethics policy, the Company's policies regarding trading in the Common
      Stock or any other applicable policies, rules or regulations of the
      Company which results in a Material Injury. If the Company desires to
      terminate the Executive for Cause pursuant to the provisions of this
      Section 4(a), the Executive will be given a written notice by the Board of
      the facts and circumstances providing the basis for termination for Cause,
      and the Executive will have 30 days from the date of such notice to
      remedy, cure or rectify the situation giving rise to

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      termination for Cause to the reasonable satisfaction of the Board (except
      in the event of termination for Cause pursuant to subparagraph (i) above
      as to which no cure period will be permitted).

            (b) Good Reason. After a Change in Control, the Executive may
      terminate employment with the Company at any time during the term of this
      Agreement for Good Reason, upon written notice to the Company delivered in
      accordance with Sections 4(c) and 12 hereof.

                  (i) Definition. For purposes of this definition of "Good
            Reason," the term "Company" shall mean the Company and/or its
            Affiliates. For purposes of this Agreement, "Good Reason" means (i)
            the assignment to the Executive of any duties materially
            inconsistent in any respect with the Executive's duties or
            responsibilities as contemplated in this Agreement, provided that
            the Executive specifically terminates his employment for Good Reason
            hereunder within 120 days from the date that he has actual notice of
            such material breach; (ii) any other action by the Company which
            results in a material diminishment in the Executive's position
            (including status, offices, titles and reporting requirements),
            authority, duties or responsibilities, provided that the Executive
            specifically terminates his employment for Good Reason hereunder
            within 120 days from the date that he has actual notice of such
            material breach; (iii) any breach by the Company of any of the
            provisions of this Agreement, provided that the Executive
            specifically terminates his employment for Good Reason hereunder
            within 120 days from the date that he has actual notice of such
            material breach; (iv) requiring the Executive to relocate to any
            office or location other than Houston, Texas, without his consent;
            (v) a 5% or more reduction, or attempted reduction, at any time
            during the Executive's employment with the Company, of the base
            salary of the Executive unless such reduction is also applied to all
            other executives of the Company; or (vi) the taking of any action by
            the Company which would adversely affect the Executive's
            participation in or materially reduce the Executive's benefits
            provided under the Company's welfare benefit plans, unless (A) there
            is substituted a comparable benefit that is at least economically
            equivalent (in terms of the benefit offered to the Executive) to the
            benefit in which the Executive's participation is being adversely
            affected or to the Executive's benefits that are being materially
            reduced, or (B) the taking of such action affects all other
            executives of the Company. Notwithstanding the preceding provisions
            of this Section 4(b), if the Executive desires to terminate his
            employment for Good Reason, he shall first give written notice of
            the facts and circumstances providing the basis for Good Reason to
            the Board or the Compensation Committee thereof, and allow the
            Company thirty (30) days from the date of such notice to remedy,
            cure or rectify the situation giving rise to Good Reason to the
            reasonable satisfaction of the Executive.

                  (ii) Determination by the Executive Presumed Correct. Any
            determination by the Executive pursuant to this Section 4(b) that
            Good Reason exists for the Executive's termination of employment and
            that adequate remedy has not occurred shall be presumed correct and
            shall govern unless the party

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            contesting the determination shows by a clear preponderance of the
            evidence that it was not a good faith reasonable determination.

                  (iii) Severance Payment Made Notwithstanding Dispute.
            Notwithstanding any dispute concerning whether Good Reason exists
            for termination of employment or whether adequate remedy has
            occurred, the Company shall immediately pay to the Executive, as
            specified in Section 5 hereof, any amounts otherwise due under this
            Agreement. The Executive may be required to repay such amounts to
            the Company if any such dispute is finally determined adversely to
            the Executive.

            (c) Notice of Termination. Any termination of the Executive's
      employment by the Company or by the Executive hereunder, shall be
      communicated by Notice of Termination to the other party hereto given in
      accordance with this Agreement. For purposes of this Agreement, a "Notice
      of Termination" means a written notice which (i) indicates the specific
      termination provision in this Agreement relied upon, (ii) sets forth in
      reasonable detail the facts and circumstances claimed to provide a basis
      for termination of the Executive's employment under the provision so
      indicated and (iii) specifies the termination date, if such date is other
      than the date of receipt of such notice (which termination date shall not
      be more than 15 days after the giving of such notice, unless otherwise
      provided herein). Notwithstanding the foregoing, the Company may elect to
      consider the Executive as an employee after the date of termination for
      purposes of complying with the provisions of Section 5 hereof.

      5. Severance Payment Upon Termination of Employment. If the Executive's
employment with the Company is terminated during the term of this Agreement and
after a Change in Control (a) by the Company other than for Cause, or (b) by the
Executive for Good Reason, then the Executive shall be entitled to the
following:

            (a) The Company shall pay to the Executive in a lump sum in cash
      within five (5) days after date of termination, if not theretofore paid,
      the Executive's base salary (as in effect on the date of termination)
      through the date of termination, and in the case of compensation
      previously deferred and bonuses previously earned by the Executive, all
      amounts of such compensation previously deferred and earned and not yet
      paid by the Company.

            (b) The Company shall, promptly upon submission by the Executive of
      supporting documentation, pay or reimburse to the Executive any costs and
      expenses paid or incurred by the Executive which would have been payable
      pursuant to the Company's policy regarding the reimbursement of such costs
      or expenses as in effect from time to time during the Executive's
      employment with the Company if the Executive's employment had not
      terminated.

            (c) The Company shall pay to the Executive in a lump sum in cash
      within five (5) days after the date of termination a severance payment
      equal to one and one-half (1.5) times the sum of (i) the Executive's base
      salary (as in effect on date of termination) and (ii) the Executive's most
      recent annual bonus. If the most recent annual bonus was a

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      stock option or a stock grant, the value of the bonus will be deemed to be
      the number of option shares times the closing price of the Common Stock
      for the 20 trading days prior to the date of termination.

            (d) During the 18-month period commencing on the date of
      termination, the Company shall continue benefits (other than disability
      benefits), at the Company's expense to the Executive and/or the
      Executive's family at least equal to those which would have been provided
      to them under the Company's welfare benefit plans if the Executive's
      employment had not been terminated (without giving effect to any reduction
      in such benefits subsequent to the Change in Control which reduction
      constitutes or may constitute Good Reason).

      6. Certain Payments by the Company

            (a) In the event that the Executive is deemed to have received an
      "excess parachute payment" (as defined in Section 280G(b) of the Internal
      Revenue Code of 1986, as amended, and the rules and regulations
      promulgated by the Internal Revenue Service thereunder (the "Code")) which
      is subject to the excise taxes (the "Excise Taxes") imposed by Section
      4999 of the Code in respect of any payment pursuant to this Agreement or
      any other agreement, plan, instrument or obligation, in whatever form, the
      Company shall make the Bonus Payment (defined below) to the Executive
      notwithstanding any contrary provision in this Agreement or any other
      agreement, plan, instrument or obligation.

            (b) The term "Bonus Payment" means a cash payment in an amount equal
      to the sum of (i) all Excise Taxes payable by the Executive, plus (ii) all
      additional Excise Taxes and federal or state income taxes to the extent
      such taxes are imposed in respect of the Bonus Payment, such that the
      Executive shall be in the same after-tax position and shall have received
      the same benefits that he would have received if the Excise Taxes had not
      been imposed. For purposes of calculating any income taxes attributable to
      the Bonus Payment, the Executive shall be deemed for all purposes to be
      paying income taxes at the highest marginal federal income tax rate,
      taking into account any applicable surtaxes and other generally applicable
      taxes which have the effect of increasing the marginal federal income tax
      rate and, if applicable, at the highest marginal state income tax rate, to
      which the Bonus Payment and the Executive are subject. An example of the
      calculation of the Bonus Payment is set forth below. Assume that the
      Excise Tax rate is 20%, the highest federal marginal income tax rate is
      40% and the Executive is not subject to state income taxes. Further assume
      that the Executive has received an excess parachute payment in the amount
      of $200,000, on which $40,000 ($200,000 x 20%) in Excise Taxes are
      payable. The amount of the required Bonus Payment is thus computed to be
      $100,000, i.e., the Bonus Payment of $100,000, less additional Excise
      Taxes on the Bonus Payment of $20,000 (i.e., 20% x $100,000) and income
      taxes of $40,000 (i.e., 40% x $100,000), yields $40,000, the amount of the
      Excise Taxes payable in respect of the original excess parachute payment.

            (c) The Executive agrees to reasonably cooperate with the Company to
      minimize the amount of the excess parachute payments, including, without
      limitation,

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      assisting the Company in establishing that some or all of the payments
      received by the Executive that are "contingent on a change," as described
      in Section 280G(b)(2)(A)(i) of the Code, are reasonable compensation for
      personal services actually rendered by the Executive before the date of
      such change or to be rendered by the Executive on or after the date of
      such change. In the event that the Company is able to establish that the
      amount of the excess parachute payments is less than originally
      anticipated by the Executive, the Executive shall refund to the Company
      any excess Bonus Payment to the extent not required to pay Excise Taxes or
      income taxes (including those incurred in respect of receipt of the Bonus
      Payment). Notwithstanding the foregoing, the Executive shall not be
      required to take any action which his attorney or tax advisor advises him
      in writing (i) is improper or (ii) exposes the Executive to personal
      liability. The Executive may require the Company to deliver to the
      Executive an indemnification agreement in form and substance reasonably
      satisfactory to the Executive as a condition to taking any action required
      by this Section 6(c).

            (d) The Company shall make any payment required to be made under
      Section 6 hereof in a cash lump sum after the date on which the Executive
      received or is deemed to have received any such excess parachute payment.
      Any payment required to be paid by the Company under Section 6 hereof
      which is not paid within 30 days of receipt by the Company of the
      Executive's written demand therefor, delivered in accordance with Section
      12 hereof, shall thereafter be deemed delinquent, and the Company shall
      pay to the Executive immediately upon demand interest at the highest
      nonusurious rate per annum allowed by applicable law from the date such
      payment becomes delinquent to the date of payment of such delinquent sum
      with interest.

            (e) In the event that there is any change to the Code which results
      in the recodification of Section 280G or Section 4999 of the Code, or in
      the event that either such section of the Code is amended, replaced or
      supplemented by other provisions of the Code of similar import ("Successor
      Provisions"), then this Agreement shall be applied and enforced with
      respect to such new Code provisions in a manner consistent with the intent
      of the parties as expressed herein, which is to assure that the Executive
      is in the same after-tax position and has received the same benefits that
      he would have been in and received if any taxes imposed by Section 4999
      (or any Successor Provisions) had not been imposed.

            (f) All determinations required to be made under Section 6 hereof
      including, without limitation, whether and when a Bonus Payment is
      required, and the amount of such Bonus Payment and the assumptions to be
      utilized in arriving at such determinations, unless otherwise expressly
      set forth in this Agreement, shall be made within 30 days from the date of
      termination by the independent tax consultant(s) selected by the Company
      and reasonably acceptable to the Executive (the "Tax Consultant"). The Tax
      Consultant must be a qualified tax attorney or certified public
      accountant. All fees and expenses of the Tax Consultant shall be paid in
      full by the Company. Any Excise Taxes as determined pursuant to Section 6
      hereof shall be paid by the Company to the Internal Revenue Service or any
      other appropriate taxing authority on the Executive's behalf within five
      (5) business days after receipt of the Tax Consultant's final
      determination by the Company and the Executive.

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            (g) If the Tax Consultant determines that there is substantial
      authority (within the meaning of Section 6662 of the Code) that no Excise
      Taxes are payable by the Executive, the Tax Consultant shall furnish the
      Executive with a written opinion that failure to disclose or report the
      Excise Taxes on the Executive's federal income tax return will not
      constitute a substantial understatement of tax or be reasonably likely to
      result in the imposition of a negligence or any other penalty.

            (h) The Company shall indemnify and hold harmless the Executive, on
      an after-tax basis, from any costs, expenses, penalties, fines, interest
      or other liabilities ("Losses") incurred by the Executive with respect to
      the exercise by the Company of any of its rights under Section 6 hereof,
      including, without limitation, any Losses related to the Company's
      decision to contest a claim of any imputed income to the Executive. The
      Company shall pay all fees and expenses incurred under Section 6 hereof,
      and shall promptly reimburse the Executive for the reasonable expenses
      incurred by the Executive in connection with any actions taken by the
      Company or required to be taken by the Executive hereunder. Any payments
      owing to the Executive and not made within 30 days of delivery, in
      accordance with Section 12 hereof, to the Company of evidence of the
      Executive's entitlement thereto shall be paid to the Executive together
      with interest at the maximum nonusurious rate permitted by law.

      7. Reimbursement of Legal Costs. The Company shall pay to the Executive
all legal fees and expenses incurred by the Executive as a result of a
termination which entitles the Executive to any payments under this Agreement
including all such fees and expenses, if any, incurred in contesting or
disputing any notice of termination under Section 4(a) hereof or in seeking to
obtain or enforce any right or benefit provided by this Agreement. Such payments
shall be made within five (5) days after delivery of the Executive's respective
written requests for payment accompanied by such evidence of fees and expenses
incurred as the Company reasonably may require.

      8. Damages. The Executive shall not be required to mitigate damages with
respect to the amount of any payment provided under this Agreement by seeking
other employment or otherwise, nor shall the amount of any payment provided
under this Agreement be reduced by retirement benefits, deferred compensation or
any compensation earned by the Executive as a result of employment by another
employer.

      9. Successor to the Company. The Company shall require any successor or
assign (whether direct or indirect, by purchase, merger, consolidation or
otherwise) to all or substantially all of the business and/or assets of the
Company, by agreement in form and substance satisfactory to the Executive,
expressly, absolutely and unconditionally to assume and agree to perform this
Agreement in the same manner and to the same extent that the Company would be
required to perform it if no such succession or assignment had taken place. A
used in this Agreement, "Company" shall mean the Company as hereinbefore defined
and any successor or assign to its business and/or assets as aforesaid which
executes and delivers the agreement provided for in this section or which
otherwise becomes bound by all the terms and provisions of this Agreement by
operation of law.

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      10. Heirs of the Executive. This Agreement shall inure to the benefit of
and be enforceable by the Executive's personal and legal representatives,
executors, administrators, successors, heirs, distributees, devisees and
legatees. If the Executive should die while any amounts are still payable to the
Executive hereunder, all such amounts, unless otherwise provided herein, shall
be paid in accordance with the terms of this Agreement to the Executive's
devisee, legatee, or other designee or, if there be so much designee, to the
Executive's estate.

      11. Arbitration. Any dispute, controversy or claim arising under or in
connection with this Agreement, or the breach thereof, shall be settled
exclusively by arbitration in accordance with the Rules of the American
Arbitration Association then in effect. Judgment upon the award rendered by the
arbitrator(s) may be entered in any court of competent jurisdiction. Any
arbitration held pursuant to this section in connection with the Executive's
termination of employment shall take place in Houston, Texas at the earliest
possible date. If any proceeding is necessary to enforce or interpret the terms
of this Agreement, or to recover damages for breach thereof, the prevailing
party shall be entitled to reasonable attorneys' fees and necessary costs and
disbursements, not to exceed in the aggregate one percent (1%) of the net worth
of the other party, in addition to any other relief to which he or it may be
entitled.

      12. Notice. All notices and other communications required or permitted
hereunder or necessary or convenient in connection herewith shall be in writing
and shall be deemed to have been given when (i) delivered by hand or sent by
facsimile, or (ii) on the third business day following deposit in the United
States mail by registered or certified mail, return receipt requested, to the
addresses as follows (provided that notice of change of address shall be deemed
given only when received):

            If to the Company to:

            Texas Biotechnology Corporation
            7000 Fannin
            Houston, Texas 77030
            Attention: President and Chief Executive Officer
            Facsimile No.: (713) 782-8232

            If to the Executive to:

            Name: _____________________
            Texas Biotechnology Corporation
            7000 Fannin
            Houston, Texas 77030
            Facsimile No.: (713) 782-8232

or to such other names or addresses as the Company or the Executive, as the case
may be, shall designate by notice to the other party hereto in the manner
specified in this Section 12.

      13. General Provisions.

            (a) The Executive's rights and obligations under this Agreement
      shall not be transferable by assignment or otherwise, nor shall the
      Executive's rights be subject to

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      encumbrance or subject to the claims of the Company's creditors. Nothing
      in this Agreement shall prevent the consolidation of the Company with, or
      its merger into, any other corporation, or the sale by the Company of all
      or substantially all of its properties or assets; and this Agreement shall
      inure to the benefit of, be binding upon and be enforceable by, any
      successor surviving or resulting corporation, or other entity to which
      such assets shall be transferred. This Agreement shall not be terminated
      by the voluntary or involuntary dissolution of the Company.

            (b) This Agreement and any employment agreement with the Executive
      plus terms of any stock option plans or grants constitutes the entire
      agreement between the parties hereto in respect to the rights and
      obligations of the parties following a Change in Control. This Agreement
      supersedes and replaces all prior oral and written agreements,
      understandings, commitments, and practices between the parties (whether or
      not fully performed by the Executive prior to the date hereof), which
      shall be of no further force or effect.

            (c) The provisions of this Agreement shall be regarded as divisible,
      and if any of said provisions or any part thereof are declared invalid or
      unenforceable by a court of competent jurisdiction, the validity and
      enforceability of the remainder of such provisions or parts thereof and
      the applicability thereof shall not be affected thereby.

            (d) This Agreement may not be amended or modified except by a
      written instrument executed by the Company and the Executive.

            (e) This Agreement and the rights and obligations hereunder shall be
      governed by and construed in accordance with the laws of the State of
      Texas.

      IN WITNESS WHEREOF, the undersigned, intending to be legally bound, have
executed this Agreement as of the date first written above.

                                   Texas Biotechnology Corporation

                                   By:
                                       -------------------------------------
                                       Bruce D. Given, M.D.
                                       President and Chief Executive Officer

                                   Executive:

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

                                       10<PAGE>
                                                                   Exhibit 10.21

                       THIRD AMENDMENT TO LEASE AGREEMENT

      THIS THIRD AMENDMENT TO LEASE AGREEMENT ("Amendment") is entered into by
and between the BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM ("Landlord"),
and TEXAS BIOTECHNOLOGY CORPORATION ("Tenant"), to be effective as of January 1,
2003.

                                    RECITALS

      A. Doctors Center Inc. ("DC") and Tenant entered into a Lease Agreement
("Lease") dated February 24, 1995, by which DC leased to Tenant approximately
28,909 square feet of net rentable area in the building then known as Doctors
Center Office Building and located at 7000 Fannin Street in Houston, Harris
County, Texas (the "Building").

      B. Landlord acquired the Building on May 31, 1996, including DC's interest
in the Lease.

      C. Landlord and Tenant have subsequently entered into Amendments to the
Lease dated April 1, 1999 and January 1, 2001, and a renewal option, which was
exercised June 30, 2000 covering approximately 37,500 square feet of net
rentable area in the Building. The original Lease Agreement, as amended by the
previous amendments, is hereinafter referred to as the "Lease."

      D. Landlord and Tenant wish to amend the Lease to (1) modify the
description of the leased Premises to delete certain administrative space on the
20th floor of the Building, which will be surrendered by Tenant; (2) add a
renewal option for Tenant to extend the Term for one additional two-year period;
(3) specify a Base Rent rate for the extension period; and (4) provide for
leasing certain storage space in the Building to Tenant.

      E. Landlord and Tenant wish to enter into this Amendment to evidence the
modification of the Lease on the terms and conditions stated below.

                              TERMS AND CONDITIONS

      NOW, THEREFORE, in consideration of the mutual covenants contained herein,
and for other good and valuable consideration, the receipt and legal sufficiency
of which are hereby acknowledged by the parties, Landlord and Tenant hereby
agree as follows:
<PAGE>

      1. Defined Terms. Capitalized terms that are not otherwise defined in this
Amendment have the respective meanings assigned to them in the Lease.

      2. Reduction of Lease Space. Tenant shall vacate and surrender to Landlord
approximately 6,141 square feet of net rentable area on the 20th floor of
Building (the "Contraction Space") no later than January 31, 2003 (the
"Surrender Date"). The Contraction Space is more particularly described in
EXHIBIT B-1 attached to this Amendment, and hereby made a part of the Lease. On
or before the Surrender Date, Tenant shall, at its sole expense, (a) remove from
the Contraction Space all of Tenant`s personal property, (b) surrender
possession of the Contraction Space to Landlord in good order and condition, and
(c) make repairs as necessitated by removal of Tenant's property, all in
accordance with the provisions in Section 9.1 of the Lease.

      3. Renewal of Lease Term. As long as Tenant is not in default under the
Lease, Tenant shall have the option to renew this Lease upon the terms and
conditions herein stated for one renewal period of two years commencing on
January 1, 2006, and expiring on December 31, 2007 (the "Extended Term"), unless
further extended or sooner terminated as provided in this Lease. To renew this
Lease, Tenant must give written notice to Landlord no later than December 31,
2003.

      4. Payment of Rental. The Base Rent during the Extended Term shall be
calculated at a rate of $28 per net rentable square foot per year, payable in
advance as provided in the Lease. Adjustments to Base Rent will be calculated
using 2005 as the base year.

      5. Storage Space. Sections 2 and 3 of the Amendment to Office Lease
Agreement between Landlord and Tenant dated effective January 1, 2001, are
hereby deleted and replaced with the following paragraph, which shall become a
part of the Lease:

      Landlord leases to Tenant and Tenant leases from Landlord that certain
      storage space in those areas in the Building identified in the attached
      EXHIBIT B-2 (the "Storage Space"). The term of the lease for the Storage
      Space shall be month-to-month, and may be terminated by either Landlord or
      Tenant on thirty (30) days notice to the other party. Tenant's leasehold
      in the Storage Space shall automatically terminate upon expiration of the
      Term of the Lease, or upon an earlier termination of the Lease for any
      reason. In addition to the Rent payable for the leased Premises, Tenant
      shall pay rent for the Storage Space in advance as provided in the Lease,
      and at the rates stated in EXHIBIT B-2. Tenant shall use the Storage Space
      only for the purpose of storing goods, in accordance with the terms and
      conditions of the Lease and the additional terms and conditions for the
      Storage Space specified in the attached EXHIBIT B-3. The EXHIBIT B-2 and
      EXHIBIT B-3 attached to this Amendment are hereby incorporated as parts of
      the Lease, and are designated as EXHIBIT B-2 and EXHIBIT B-3 to the Lease,
      respectively.

<PAGE>

      6. Performance of and Compliance with the Terms and Conditions of the
Lease. Landlord and Tenant each promise and agree to perform and comply with the
terms, provisions, and conditions of and the agreements in the Lease, as
modified by this Amendment.

      7. Ratification and Reaffirmation of Lease. Landlord and Tenant each
hereby ratify, affirm, and agree that the Lease, as herein modified, represents
the valid, binding and enforceable obligations of Landlord and Tenant,
respectively.

      8. Continuation of Lease. Except as expressly stated in this Amendment,
the terms of the Lease shall remain unchanged and in full force and effect as
originally provided.

      9. Applicable Law. Landlord and Tenant hereby agree that this Amendment
and the Lease shall be governed and construed according to the laws of the State
of Texas from time to time in effect.

      10. Inurement. This Amendment shall be binding on and inure to the benefit
of Landlord and Tenant and their respective heirs, executors, administrators,
legal representatives, successors and assigns.

      11. No Commission. Landlord and Tenant each warrant and represent to the
other that no commission or fee is due or will be paid in connection with this
Amendment.

      12. Entirety and Amendments. The Lease, as expressly modified by this
Amendment, constitutes the sole and only agreement of the parties to the Lease
and supersedes any prior understandings or written or oral agreements between
the parties concerning the lease of the Premises. The Lease may be amended or
supplemented only by an instrument in writing executed by the party against whom
enforcement is sought.

      13. Construction. Each party acknowledges that it and its counsel have
reviewed this Amendment and that the normal rule of construction shall not be
applicable and there shall be no presumption that any ambiguities will be
resolved against the drafting party in interpretation of this Amendment.

      14. Authority. Tenant warrants and represents that (a) Tenant has the full
right, power and authority to enter into this Amendment, (b) all requisite
action to authorize Tenant to enter into this Amendment and to carry out
Tenant's obligations hereunder has been taken, and (c) the person signing on
behalf of Tenant has been duly authorized by Tenant to sign this Amendment on
its behalf.

      15. Paragraph Headings. The paragraph headings used herein are intended
for reference purposes only and shall not be considered in the interpretation of
the terms and conditions hereof.

<PAGE>

      16. Counterparts. This Amendment may be executed in any number of
counterparts, all of which taken together shall constitute one and the same
agreement, and any of the parties to this Amendment may execute the Amendment by
signing any of the counterparts.

      In witness whereof, this Amendment is executed to be effective as of the
date first set forth above.

LANDLORD:                                       TENANT:

BOARD OF REGENTS OF                             TEXAS BIOTECHNOLOGY
THE UNIVERSITY OF TEXAS SYSTEM                  CORPORATION

By: /s/ James S. Wilson                         By: /s/ Bruce D. Given, M.D.
    -------------------------------------          -------------------------
        James S. Wilson
        Executive Director of Real Estate       Name: Bruce D. Given, M.D.
        The University of Texas System               -----------------------
                                                Title: President and CEO
                                                      ----------------------
<PAGE>

                                   EXHIBIT B-2

                               TO LEASE AGREEMENT

Description of Storage Space leased by Lessee in the Building:

<TABLE>
<CAPTION>
                                    Room No.         Square Footage    Rate
                                    --------         --------------    ----
<S>                                 <C>              <C>               <C>
Additional Space #1                 P2-8             approx. 450       $531/month

Additional Space #2                 P5-6             approx. 77        $38.50/month

Additional Space #3                 P5-12            approx. 114       $65.50/month
</TABLE>

<PAGE>

                                   EXHIBIT B-1

                               TO LEASE AGREEMENT

        Depiction or Description of Contraction Space in leased Premises
<PAGE>

                                   EXHIBIT B-3
                                       TO
                                 LEASE AGREEMENT

Additional Terms and Conditions applicable to use of Storage Space:

Tenant warrants and represents to Landlord that the Storage Space shall be used
and occupied only for the purpose of STORAGE OF GOODS.

Tenant and Landlord understand that Additional Space #1 and Additional Space #2
are to be utilized for the decay of radioactive waste materials. Tenant warrants
and represents that such materials are handled in accordance with all laws,
ordinances, rules and regulations of any governmental authorities having
jurisdication with respect to hazardous materials and with the provisions of the
Lease related to hazardous materials. Tenant further warrants that the handling
of such materials is in compliance with the requirements of Tenant's Radioactive
Materials License.

Tenant shall use and occupy the Storage Space, conduct its business, and control
its agents and employees in such a way as is lawful, reputable, and will not
create any nuisance or otherwise interfere with, annoy, or disturb any other
tenant in its normal business operations.

Tenant shall not commit, or suffer to be committed, any waste in the Storage
Space, nor shall Tenant permit the Storage Space to be used in any way which
would, in the opinion of the Landlord, create a hazardous or unsightly
environment.

Tenant shall (1) place any waste items that are not equipment or non-goods that
can be recycled in a recycling bin provided by the management of the Building
and (2) remove from the Building all items that are waste and not considered
items for recycling.

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