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Bioprocessing Services Agreement - EntreMed Inc. and Covance Biotechnology Services Inc.

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                                                      EntreMed-Covance Agreement

                       BIOPROCESSING SERVICES AGREEMENT

This manufacturing services agreement dated this 7th day of July 1999 (the
"Agreement") between EntreMed, Inc. a Delaware corporation ("Sponsor") having
its principal place of business at 9640 Medical Center Drive, Rockville, MD
20850 and Covance Biotechnology Services Inc., a Delaware Corporation ("CBSI"),
having its principal place of business at 6051 George Watts Hill Drive, P. O.
Box 13865, Research Triangle Park, NC 27709-3865.

WITNESSETH
WHEREAS, CBSI provides a full range of bioprocessing services to the
biopharmaceutical industry, including process development, fermentation, cell
culture, separation/purification, bioanalytical chemistry, quality control,
quality assurance, and regulatory affairs.

WHEREAS, sponsor desires CBSI to perform services in accordance with the terms
of this Agreement and the Scope of Work (as hereinafter defined) related to the
production of the material known as Angiostatin(TM) (the "Product") and CBSI
desires to perform such services.

NOW, THEREFORE, in consideration of the above statements and other good and
valuable consideration, the sufficiency and receipt of which are hereby
acknowledged, the parties hereto agree as follows:


Section 1.
SCOPE OF WORK
a)    A detailed Scope of Work document ("Scope") to be provided by Sponsor or
      prepared by CBSI under Sponsor's direction and approved by Sponsor will be
      attached to this agreement as Appendix 1. CBSI will perform the service or
      services ("Program") for Sponsor in accordance with the Scope. The Scope
      will specify the program design, information desired, estimated duration
      of the Program, and all other matters pertinent to completion of the
      Program, and will be deemed a part of this Agreement and is incorporated
      herein by reference.

b)    CBSI will, at Sponsor's request, consult with Sponsor in developing the
      Program design in a manner consistent with current regulatory guidelines.
      However, CBSI does not warrant that the Product will be safe or
      efficacious or that the CMC section prepared as result of performing the
      Program will satisfy all the requirements of any regulatory agencies at
      the time of submission.

c)    CBSI's performance of the work will be based on technical information
      provided by or for the Sponsor. This information will be translated into
      development and/or manufacturing documents (development plans, batch
      records, specifications, etc.) which will be reviewed and approved by the
      Sponsor. These documents will form the basis upon which the work will be
      performed.


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Section 2.
PROGRAM PERFORMANCE
CBSI shall use commercially reasonable efforts to provide facilities, supplies,
and staff necessary to complete the Program as provided in the Scope, as it may
be modified as provided herein, and in accordance with the terms of this
Agreement. In the event of any conflict between the Scope/Program and this
Agreement, the terms of this Agreement shall control.

CBSI will appoint a CBSI representative (the "Program Manager") to be
responsible for the completion of the Program by CBSI. The Program Manager will
coordinate performance of the Program with a representative designated by
Sponsor (the "Sponsor Representative"), which representative shall have
responsibility over all matters relating to performance of the Program on behalf
of Sponsor. Unless otherwise agreed in the Scope, all communications between
CBSI and the Sponsor regarding the conduct of the Program pursuant to the Scope
shall be addressed to or routed through the Program Manager and Sponsor
Representative, directly. CBSI may, at its option, substitute the Program
Manager during the course of the program.

Section 3.
PROGRAM MATERIALS
a)    Sponsor will provide CBSI with sufficient amounts of raw materials or
      other substances with which to perform the Program as specified in the
      Scope, (the "Materials"), as well as all documentation and such other data
      as may be available to apprise CBSI of the stability of the Materials,
      process characteristics, proper storage, manufacturing and safety
      requirements. Sponsor will also provide CBSI with all necessary
      information to effect the reliable transfer of the process from the
      Sponsor to CBSI.

b)    Upon completion of the Program, any remaining samples of the Materials or
      other substances provided to CBSI will be returned to Sponsor, at
      Sponsor's option and/or retained by CBSI in compliance with regulatory
      requirements.

Section 4.
COMPLIANCE WITH GOVERNMENT REGULATIONS
a)    CBSI will perform the Program in accordance with the Scope, and the
      current state of the Food and Drug Administration's current Good
      Manufacturing Practices (cGMP's) when appropriate to do so. Subject to
      paragraph b. of Section 4 below, CBSI will also comply in all material
      respects with all applicable government regulatory requirements concerning
      current Good Manufacturing Practices appropriate to the Program.

b)    Should such government regulatory requirements be changed, CBSI will make
      every reasonable effort to satisfy the new requirements. In the event that
      compliance with such new regulatory requirements necessitates a change in
      the Scope for the Program, CBSI


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      will submit to Sponsor a revised technical and cost proposal for Sponsor's
      acceptance prior to making any changes in the Scope or the Program.

c)    In the event of a conflict in government regulations, Sponsor will
      designate, in writing, which regulations shall be followed by CBSI in its
      performance of the Program.

Section 5.
FACILITY VISITS
Sponsor's representatives may visit CBSI's facility at appropriate times
consistent with the Program to observe the progress of the Program. CBSI will
assist Sponsor in scheduling such visits which will be in compliance with
requirement to protect confidentiality of other clients.

Section 6.
COMPENSATION
a)    The estimated budget for the Program is as provided in the Scope (Appendix
      1). Such budget is subject to adjustment if (1) Sponsor executes this
      Agreement later than 30 days after the date CBSI has executed this
      Agreement and (2) the Materials or other data or information required to
      conduct the Program is supplied or provided more than 30 days after the
      date CBSI has executed this Agreement.

b)    Sponsor shall make payments as defined in the Payment Schedule included in
      Appendix 1. A "..." fee equal to "..." will be added to "...". The "..."
      fee will be waived on "...". "..." charges, such as for "...", will be
      invoiced "...". Payments are due 30 days from the date of invoice. Late
      payments are subject to an interest charge of "...". Any payments that are
      greater than 90 days past due constitute a breach of this Agreement unless
      there is a dispute relative to such payments which has not yet been
      resolved pursuant to Section 14.

c)    In the event that "...", "..." shall "..." for "..." at the rate of "...".

Section 7.
CHANGE ORDERS
a)    The estimated budget for the Program specified in Section 6 of this
      Agreement and the individual budget components and time estimates
      specified in the Scope are subject to a number of general and program
      specific assumptions. The program specific assumptions relate to
      the Program design and objectives, manpower requirements, timing, capital
      expenditure requirements, if any, and other matters relating to the
      completion of the Program as set forth in the Scope (the "Program
      Assumptions"). CBSI also assumes that the Sponsor will cooperate and
      perform its obligations under the Agreement and Scope in a timely manner,
      that no event outside the control of CBSI will occur, including, without
      limitation, the events described in Section 17, and that there are no
      material changes to any applicable laws, rules or regulations which effect
      the Program (the foregoing assumptions together with the Program
      Assumptions, collectively, the "Assumptions")


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      In the event that any of the Assumptions require modification or the
      Program objectives cannot be achieved based on the Assumptions (each
      being, a "Modification") then the Scope may be amended as provided in
      paragraph b) of this Section 7.

b)    In the event a Modification is identified by the Sponsor or by CBSI, the
      identifying party shall notify the other party as soon as is reasonably
      possible. CBSI shall provide Sponsor with a Change Order containing an
      estimate of the required Modifications to the Program budget and timeline
      specified in the Scope within 20 business days of receiving such notice.
      Sponsor shall use best efforts to respond in writing to such Change Order
      promptly. If Sponsor does not approve such Change Order and has not
      terminated the Program but wants the Program to be modified to take into
      account the Modification, then Sponsor and CBSI shall use best efforts to
      agree on a Change Order that is mutually acceptable. If practicable, CBSI
      shall continue work on the Program during any such negotiations, but shall
      not commence work with respect to the Change Order unless authorized in
      writing.

Section 8.
CONFIDENTIAL INFORMATION/LEGAL PROCEEDINGS
a)    CBSI will not disclose, without Sponsor's written permission, any
      information pertaining to Sponsor's Program unless such disclosure: 1) is
      to an affiliate of CBSI who is under a similar obligation to keep such
      information confidential; 2) is or becomes publicly available through no
      fault of CBSI; 3) is disclosed by a third party entitled to disclose it;
      4) is already known to CBSI as shown by its prior written records; or 5)
      is required by any law, rule, regulation, order decision, decree, subpoena
      or other legal process to be disclosed. If such disclosure is requested by
      legal process, CBSI will make all reasonable efforts to notify Sponsor of
      this request promptly prior to any disclosure to permit Sponsor to oppose
      such disclosure by appropriate legal action.

b)    CBSI will not transfer any materials without Sponsor's written permission
      to any third party unless such transfer is to an affiliate bound by the
      terms herein and is consistent with the Program.

c)    If CBSI shall be obliged to provide testimony or records regarding any
      Sponsor Program in any legal or administrative proceeding, then Sponsor
      shall reimburse CBSI its out-of-pocket costs therefore plus an hourly fee
      for its employees or representatives equal to the internal fully burdened
      costs to CBSI of such employee or representative.

Section 9.
WORK PRODUCT
a)    All work outputs (e.g. reports) will be prepared on CBSI's standard format
      unless otherwise specified in the Scope.

b)    Sponsor will have title to all Materials, raw data, documentation,
      records, protocols, specimens and other reports generated as a result of
      this Program. All such written


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                                                      EntreMed-Covance Agreement



      materials will be archived by CBSI for a period of five years following
      completion of the Program unless otherwise defined by the Program or
      required by applicable laws or regulations. Five years after completion of
      the Program, all of the aforementioned materials will be sent to the
      Sponsor and a reasonable return fee will be charged. The Sponsor may elect
      to have the materials retained in the CBSI Archives for an additional
      period of time at a reasonable additional cost. If the Sponsor chooses to
      have CBSI dispose of the materials, a reasonable disposal fee will be
      charged. CBSI will continue to retain such documentation and materials as
      required by regulations and as may be required by law, pertaining to such
      activities as well as for archival purposes.

Section 10.
INVENTIONS, PATENTS, AND RESULTS OF THE PROGRAM

Any product or product improvement inventions or discoveries, including new uses
for product and related patent rights which arise as a result of the work
performed by CBSI will be owned by and assigned to Sponsor and CBSI will
cooperate with Sponsor in perfecting Sponsor's interest in such intellectual
property. Any process or process improvement inventions or discoveries made
solely by CBSI which arise as a result of the work performed by CBSI and related
patent rights will be owned by CBSI. Any such process or process improvement
inventions or discoveries and related patent rights which are made jointly by
the parties shall be owned jointly by the parties. With respect to any invention
or discovery not owned by Sponsor as set forth above, CBSI hereby grants to
Sponsor an exclusive, royalty-free, paid up, perpetual, worldwide, sublicensable
license in the field of Anti-Angiogenesis under CBSI's sole and joint inventions
and related patent rights arising as a result of the work performed by CBSI
hereunder in order to make, have made, use, import, sell or offer to sell
Product.


Section 11.
INDEPENDENT CONTRACTOR
CBSI shall perform the Program as an independent contractor of Sponsor and shall
have complete and exclusive control over its facilities, equipment, employees
and agents. Nothing in this agreement or other arrangements for which it is made
shall constitute CBSI, or anyone furnished or used by CBSI in the performance of
the services, as employee, joint venture, partner, or servant of Sponsor.

Section 12.
INSURANCE
CBSI shall secure and maintain in full force and effect throughout the
performance of the Program policies of insurance for (a) Workmen's Compensation,
(b) General Liability, (c) Automobile Liability, and (d) Professional Liability
having policy limits, deductibles and other terms appropriate to the conduct of
CBSI's business in CBSI's sole and exclusive judgment. Certificates evidencing
such insurance will be made available for examination upon request of the
Sponsor.



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Section 13.
DEFAULT
a)    If CBSI is in default of its material obligations under this Agreement,
      then Sponsor shall promptly notify CBSI in writing of any such default.
      CBSI shall have a period of 45 days from the date of receipt of such
      notice within which to cure such default; provided that if such default
      renders the Program invalid, then CBSI, shall, at Sponsor's option, either
      (1) repeat the Program at its cost within a time period mutually agreed to
      by it and Sponsor or (2) refund the contract price paid by Sponsor. If
      CBSI shall fail to cure such default within the specified cure period or
      repeat the Program, as the case may be, then this Agreement shall, at
      Sponsor's option, immediately terminate. In the event of such termination,
      Sponsor's sole remedy shall be, in the case where such default has not
      rendered the Program invalid, a reduction in the total contract price for
      the Program in an amount equal to the difference between (1) the total
      contract price for the Program and (2) the value of the work properly
      performed, and, in the case where such default does render the Program
      invalid, a refund of the contract price; provided however that under no
      circumstance shall CBSI be liable to Sponsor in an amount that, in
      aggregate exceeds, the contract price paid for such Program. In the event
      that any said default is directly attributable to the grossly negligent
      acts or omissions of CBSI, the limitation of remedies set forth in this
      section 13 (a) shall not apply.

b)    If Sponsor is in default of its material obligations under this Agreement,
      CBSI shall promptly notify Sponsor in writing of any such default. Sponsor
      shall have a period of 45 days from the date of receipt of such notice
      within which to cure such default; provided that if Sponsor fails to cure
      such breach within the specified cure period, this Agreement shall, at
      CBSI's option, immediately terminate.

c)    Not withstanding anything herein to the contrary, UNDER NO CIRCUMSTANCES
      SHALL EITHER PARTY BE ENTITLED TO INCIDENTAL, INDIRECT, CONSEQUENTIAL OR
      SPECIAL DAMAGES ARISING IN CONNECTION WITH THE DEFAULT OR BREACH OF ANY
      OBLIGATION OF THE OTHER PARTY UNDER THIS AGREEMENT, THE SCOPE OR ANY
      DOCUMENTS OR APPENDICES RELATED THERETO.

Section 14.
DISPUTE RESOLUTION
a)    In the event any dispute shall arise between the Sponsor and CBSI with
      respect to any of the terms and conditions of this Agreement or the
      Protocol; then senior executives of the Sponsor and CBSI shall meet as
      promptly as practicable after notice of such dispute to resolve in good
      faith such dispute.


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b)    If the Sponsor and CBSI are unable to satisfactorily resolve the dispute,
      then such dispute shall be finally settled by an arbitrator in accordance
      with this Section 14. The arbitration will be held in or around Raleigh,
      North Carolina, and except as noted below, shall be conducted in
      accordance with the rules of the American Arbitration Association by two
      arbitrators appointed, one by each party. If the arbitrators appointed
      cannot agree on the resolution of the dispute within sixty (60) days after
      the dispute is submitted to them, they shall thereupon appoint a third
      arbitrator, and if they fail to agree upon a third arbitrator within 30
      days after a deadlock is declared by either arbitrator, a third arbitrator
      will be appointed by the American Arbitration Association upon the request
      of either arbitrator. The arbitrators shall have no authority to award
      consequential, punitive or exemplary damages or to vary from or ignore the
      terms of this Agreement and shall be bound by controlling law. Finally,
      the parties may seek judicial intervention for emergency relief, such as
      restraining orders and injunctions where appropriate.

      Any decision by the third arbitrator and either one of the other
      arbitrators shall be binding upon the parties and may be entered as final
      judgment in any court having jurisdiction. The cost of any arbitration
      proceeding shall be borne by the parties as the arbitrators shall
      determine if the parties have not otherwise agreed. The arbitrators shall
      render their final decision in writing to the parties.

Section 15.
INDEMNIFICATION

a)    CBSI shall indemnify Sponsor and its affiliates and their respective
      officers, directors and employees from any loss, cost, damage or expense
      (a "Loss") from any lawsuit, action, claim, demand, assessment or
      proceeding (a "Claim") for personal injury to Program participants or
      personal injury to any employee of Sponsor or property damage arising or
      occurring during the conduct of the Program as a result of (i) CBSI's
      negligence, gross negligence or intentional misconduct or inaction, or
      (ii) CBSI's violation, non-compliance or non-performance of any terms of
      this Agreement; provided that if such Loss or Claim arises in whole or in
      part from Sponsor's negligence, gross negligence or intentional misconduct
      or inaction, then the amount of the Loss that CBSI shall indemnify Sponsor
      for pursuant to this Section 15 shall be reduced by an amount in
      proportion to the percentage of Sponsor's responsibilities for such Loss
      determined by a court of competent jurisdiction in a final and
      non-appealable decision or in a binding settlement between the parties.

b)    Sponsor shall indemnify CBSI and its affiliates and their respective
      officers, directors, employees and agents (the "CBSI Group") from any
      Claim or Loss arising from or related to (i) personal injury to a
      participant in the Program or personal injury to any employee of the CBSI
      Group directly or indirectly caused by the raw material, Product,
      intermediates or the Program, (ii) CBSI's performance of or involvement
      with the raw material, the Product or its obligations under this Agreement
      or the Scope related thereto,


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      (iii) CBSI's performance of the Program violating or infringing on the
      patents, trademarks, tradenames, servicemarks or copyrights of any third
      party with respect to Product and the process to manufacture Product,
      Product intermediates, or raw materials relating to Product, (iv) the
      harmful or otherwise unsafe effect of the raw materials or Product,
      including, without limitation, a Claim based upon Sponsor or any other
      person's use, consumption, sale, distribution or marketing of any
      substance, including the raw material or the Product, (v) the negligence,
      gross negligence or intentional misconduct or inaction of Sponsor in the
      performance of its obligations under this Agreement or Scope related to
      the Program, or (vi) the Sponsor's violation, non-compliance or
      non-performance of any of the terms of this Agreement; provided that if
      such Loss or Claim (other than a Loss or Claim described in clause (iv)
      hereof) arises in whole or in part from CBSI's negligence, gross
      negligence or intentional misconduct or inaction, then the amount of such
      Loss that Sponsor shall indemnify the CBSI Group for pursuant to this
      Section 15 shall be reduced by an amount in proportion to the percentage
      of CBSI's responsibilities for such Loss as determined by a court of
      competent jurisdiction in a final and non-appealable decision or in a
      binding settlement between the parties. Sponsor shall not indemnify the
      CBSI Group from any Loss from any claim described in clause (iv) hereof
      arising solely from the willful misconduct or inaction of CBSI.

c)    Upon receipt of notice of any Claim which may give rise to a right of
      indemnity from the other party hereto, the party seeking indemnification
      (the "Indemnified Party") shall give written notice thereof to the other
      party, (the "Indemnifying Party") with a Claim for indemnity. Such Claim
      for indemnity shall indicate the nature of the Claim and the basis
      therefore. Promptly after a claim is made for which the Indemnified Party
      seeks indemnity, the Indemnified Party shall permit the Indemnifying
      Party, at its option and expense, to assume the complete defense of such
      Claim, provided that (i) the Indemnified Party will have the right to
      participate in the defense of any such Claim at its own cost and expense,
      (ii) the Indemnifying Party will conduct the defense of any such Claim
      with due regard for the business interests and potential related
      liabilities of the Indemnified Party and (iii) the Indemnifying Party
      will, prior to making any settlement, consult with the Indemnified Party
      as to the terms of such settlement. The Indemnified Party shall have the
      right, at its election, to release and hold harmless the Indemnifying
      Party from its obligations hereunder with respect to such Claim and assume
      the complete defense of the same in return for payment by the Indemnifying
      Party to the Indemnified Party of the amount of the Indemnifying Party's
      settlement offer. The Indemnifying Party will not, in defense of any such
      Claim, except with the consent of the Indemnified Party, consent to the
      entry of any judgment or enter into any settlement which does not include,
      as an unconditional term thereof, the giving by the claimant or plaintiff
      to the Indemnified Party of a release from all liability in respect
      thereof. After notice to the Indemnified Party of the Indemnifying Party's
      election to assume the defense of such Claim, the Indemnifying Party shall
      be liable to the Indemnified Party for such legal or other reasonable
      expenses subsequently incurred by the Indemnified Party in connection with
      the defense thereof at the request of the Indemnifying Party. As to those
      Claims with respect to which the Indemnifying Party does not elect to
      assume control of the defense,



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      the Indemnified Party will afford the Indemnifying Party an opportunity to
      participate in such defense at the Indemnifying Party's own cost and
      expense, and will not settle or otherwise dispose of any of the same
      without the consent of the Indemnifying Party.

Section 16.
REPRESENTATION
Sponsor hereby represents and warrants to CBSI that it has legal title and/or a
valid license to the raw material, expression systems and process patents and
the Product and that, to the best of its knowledge, CBSI's performance of the
Program will not violate or infringe on the patents, trademarks, tradenames,
servicemarks or copyrights of any third party.

Section 17.
FORCE MAJEURE
Either party shall be excused from performing its respective obligations under
this Agreement if its performance is delayed or prevented by any event beyond
such party's reasonable control, including, but not limited to, acts of God,
fire, explosion, weather, disease, war, insurrection, civil strife, riots,
government action, or power failure, provided that such performance shall be
excused only to the extent of and during such disability. Any time specified for
completion of performance in the Scope falling due during or subsequent to the
occurrence of any or such events shall be automatically extended for a period of
time to recover from such disability. CBSI will promptly notify Sponsor if, by
reason of any of the events referred to herein, CBSI is unable to meet any such
time for performance specified in the Scope. If any part of the Program is
invalid as a result of such disability, CBSI will, upon written request from
Sponsor, but at Sponsor's sole cost and expense, repeat that part of the Program
affected by the disability. If CBSI is likely to be unable to perform for a
period in excess of 60 days then the parties agree to negotiate in good faith a
mutually satisfactory approach to resolve the delay resulting from this
paragraph. If the parties cannot reach a mutually satisfactory approach within
60 days, then Sponsor shall be entitled to terminate this Agreement without
payment of liquidated damages (Section 20).

Section 18.
ALLOCATION OF RESOURCES
If delays in the agreed commencement or performance of the Program occur because
of the Sponsor's inability to supply CBSI with agreed Materials or any
information required to begin or perform the Program within 30 days of such
agreed time, CBSI may reallocate resources being held for performance of the
Program without incurring liability to Sponsor.

Section 19.
USE OF NAMES
Neither party shall use the name of the other party or the names of the
employees of the other party in any advertising or sales promotional material or
in any publication without prior


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written permission of such party, except Sponsor may, as required by law or
regulatory requirements, disclose that CBSI has performed the Program.

Section 20.
TERMINATION BY SPONSOR
a)    Sponsor may at any time terminate the Program prior to completion by
      giving 45 days written notice to CBSI. In such event CBSI shall comply
      with such notice to terminate work on the Program and use its best efforts
      to reduce cost to Sponsor, and Sponsor shall pay CBSI upon receipt of
      CBSI's invoice all of its costs incurred or irrevocably obligated.

c)    The termination of this Agreement for any reason shall not relieve either
      party of its obligation to the other for obligations in respect of (i)
      confidentiality of information, (ii) consents for advertising purposes and
      publications, (iii) indemnification and, (iv) compensation for services
      performed.

Section 21.
ASSIGNMENT
This Agreement shall not be assigned in whole or in part by either party without
the prior written consent of the other, which consent shall not be unreasonably
withheld or delayed except Sponsor may assign without consent in the event of a
merger, acquisition, or transfer of all of its assets related to this Agreement.
Any attempt to assign this Agreement without such consent, where required, shall
be void and of no effect subject to the limitations on assignment herein. This
Agreement shall be binding upon and inure to the benefit of the successors and
assigns of the parties hereto.

Section 22.
NOTICE
All notices to be given as required in the Agreement shall be in writing and
shall be delivered personally, sent by telecopies, or mailed either by a
reputable overnight carrier or first class mail, postage prepaid to the parties
at the addresses set forth above or such other addresses as the parties may
designate in writing. Such notice shall be effective on the date sent, if
delivered personally or sent by telecopier, the date after delivery if sent by
overnight carrier and on the date received if mailed first class.

Section 23.
CHOICE OF LAW
This Agreement shall be construed and enforced in accordance with the laws of
the State of Delaware without regard to choice of law principles.

Section 24.
WAIVER/SEVERABILITY
No waiver of any provision of this Agreement, whether by conduct or otherwise,
in any one or more instances shall be deemed to be or be construed as a further
or continuing waiver of


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any such provision, or of any other provision or condition of this Agreement. If
any provisions hereof shall be determined to be invalid or unenforceable, the
validity and effect of the other provisions of this Agreement shall not be
effected thereby.

Section 25.
ENTIRE AGREEMENT;  MODIFICATION/COUNTERPARTS
This instrument, the Confidential Disclosure Agreement with an effective date of
31 March 1998, and the Scope set forth the entire Agreement between the parties
hereto with respect to the performance of the Program by CBSI for Sponsor and as
such, supersedes all prior and contemporaneous negotiations, agreements,
representations, understandings, and commitments with respect thereto and shall
take precedence over all terms, conditions and provisions on any purchase order
form or form of order acknowledgment or other document purporting to address the
same subject matter. This Agreement shall not be waived, released, discharged,
changed or modified in any manner except by an instrument signed by the duly
authorized officers of each of the partied hereto, which instrument shall make
specific reference to this Agreement and shall express the plan or intention to
modify same. This Agreement may be executed in one or more counterparts each of
which shall be deemed an original but all of which together shall constitute one
and the same instrument.

This Agreement becomes effective and binding on both parties on and as of the
last date that the parties hereto have executed this Agreement. Should terms
contained herein be at variance with the terms and conditions specified in
Sponsor's written acceptance, then the terms and conditions contained herein
take precedence.

<TABLE>
<S>                                             <C>
ENTREMED, INC.                                   COVANCE BIOTECHNOLOGY SERVICES INC.

By:         /s/  JOHN W. HOLADAY                 By:         /s/  JOHN R. BROWN
            -----------------------                          ----------------------------------

Name:       John W. Holaday                      Name:       John R. Brown
            -----------------------                          ----------------------------------

Title:      Chairman & CEO                       Title:      President & CEO
            -----------------------                          ----------------------------------

Date:       July 7, 1999                         Date:       July 7th, 1999
            -----------------------                          ----------------------------------
</TABLE>

07/07/99                                                          Page 11 of 11


<PAGE>   12
            [ "..." indicates material has been omitted pursuant to a
     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1


                                SCOPE OF WORK FOR
                                 PRODUCTION OF
                               ANIMAL TOXICOLOGY
                                    AND cGMP
                                  ANGIOSTATIN




     PREPARED FOR:   ENTREMED, INC.
     PREPARED BY:    COVANCE BIOTECHNOLOGY SERVICES INC.
     DATED:          JULY 7, 1999




                                    1 of 27
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                                   APPENDIX 1



<TABLE>
<S>                                                                                                 <C>
TABLE OF CONTENTS


THE ANGIOSTATIN PROJECT AND OBJECTIVES                                                                  4
            Understanding of the Angiostatin Project                                                    4
            Objectives of the Angiostatin Program                                                       4
PROGRAM ASSUMPTIONS                                                                                     7
ANGIOSTATIN DEVELOPMENT ACTIVITIES                                                                      8
            Plan of Action                                                                              8
            Financial Summary                                                                          11
ANGIOSTATIN MANUFACTURING RELATED ACTIVITIES                                                           12
            Technology Transfer                                                                        12
            Cell Banking and Testing                                                                   13
            Pre-Production Activities                                                                  14
            Large Scale "..." Demonstration Runs                                                       15
            Assay Qualification                                                                        16
            cGMP Stability Studies                                                                     17
            Regulatory Support Services                                                                18
            Project Management                                                                         19
            Fill/Finish of Toxicology Material                                                         19
            Financial Summary for Fixed Price Components of Angiostatin
            Manufacturing-Related Activities                                                           21
</TABLE>



                                    2 of 27
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                                   APPENDIX 1


<TABLE>
<S>                                                                                                    <C>
ANGIOSTATIN LARGE SCALE PRODUCTION OF "..."                                                            22
            Toxicology Material Manufacturing                                                          22
            Clinical Trial Material Manufacturing                                                      24
            Quality Function                                                                           25
            Financial Summary for Angiostatin Manufacturing                                            26
ESTIMATED PAYMENT SCHEDULE                                                                             28
ACCEPTANCE SIGNATURE                                                                                   28

</TABLE>




                                    3 of 27
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                  with the Securities and Exchange Commission]

                                   APPENDIX 1




THE ANGIOSTATIN PROJECT AND OBJECTIVES


            UNDERSTANDING OF THE ANGIOSTATIN PROJECT

                  -     The product is Angiostatin, a protein consisting of
                        "..."

                  -     molecule is expressed in "..."

                  -     production clone has been selected (Clone # "...")

                  -     cell lines have been received at CBSI and have been
                        released for evaluation

                  -     fermentation process is not established at the "..."
                        scale

                  -     recovery process is not established at the "..." scale

                  -     purification process is not established at the "..."
                        scale

                  -     analytical methods are not established at CBSI

                  -     stability data is not available

                  -     product specifications are not established

                  -     productivity is not established

                  -     "..." of Angiostatin are required for use in toxicology
                        studies

                  -     toxicology material will be vialed at CBSI

                  -     "..." of Angiostatin are required for use in clinical
                        trials

                  -     IND for Phase I clinical trials is targeted to be filed
                        "..."


            OBJECTIVES FOR THE ANGIOSTATIN PROGRAM

                  CBSI recognizes the following objectives for the Angiostatin
                  program and will make all reasonable efforts to meet the
                  EntreMed's timelines.

                  -     Provide process development services for fermentation,
                        purification, formulation and analytical protein
                        chemistry (reference pages 8-11).

                  -     Manufacture and vial "..." of Angiostatin for "..." by
                        "...".

                  -     Manufacture and vial "..." of Angiostatin for "..." by
                        "...".


                                    4 of 27
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                  with the Securities and Exchange Commission]

                                   APPENDIX 1

               -     Manufacture "..." of "..." Angiostatin for "..." by
                     "...".

               -     Manufacture "..." of "..." Angiostatin for "..." by
                     "...".

               -     Support EntreMed's regulatory strategy by preparing a
                     draft CMC section for a Phase I IND filing. EntreMed's
                     targeted date for IND filing for Phase I clinical trials
                     is "...".


               Note: When manufacturing clinical material, CBSI will follow
               current Good Manufacturing Practices. CBSI will manufacture
               utilizing in process control tests to meet the specifications
               for purity, identity and safety. CBSI does not warrant that
               the material produced under cGMP will be biologically active.

               -----------------------------------------------------------------
               "...".
               -----------------------------------------------------------------


               For the Angiostatin program, CBSI will:

                  -     Attempt to reproduce and scale up fermentation, recovery
                        and purification processes to manufacture Angiostatin
                        based on information from EntreMed. Perform development
                        work as necessary

                  -     Transfer/Develop methodology and qualify assays for
                        in-process control (IPC), for release testing of
                        Angiostatin and for use in support of stability testing

                  -     Prepare "..."

                  -     Perform runs at the "..."(1) scale to determine
                        reproducibility, stability and robustness of the
                        developed fermentation, recovery and purification
                        processes

                  -     Perform runs at the "..."(2) scale to test scalability
                        of the process

                  -     Perform pre-production activities in preparation for
                        cGMP manufacturing including procurement, testing and
                        release of raw materials, preparation of cGMP
                        documentation, and equipment and facility set-up

                  -     Perform "..."at the "..."(3) scale and perform
                        subsequent recovery and purification to demonstrate
                        feasibility of the process at large scale

                  -     Perform toxicology lot production at the "..." scale and
                        subsequent purification to produce a total of "..." of
                        Angiostatin (number of runs to be determined)


-----------------------------------

                  (1) "..." working volume

                  (2) "..." working volume

                  (3) "..." working volume


                                    5 of 27
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                  with the Securities and Exchange Commission]

                                   APPENDIX 1

                  -     Perform sufficient number of clinical runs at the "..."
                        scale and perform subsequent recovery and purification
                        to obtain "..." of cGMP Angiostatin

                  -     Perform fill/finish activities for toxicology material

                  -     Perform Quality Control testing and Quality Assurance
                        activities in support of release of bulk-filled Phase I
                        Angiostatin

                  -     Provide manufacturing and QC/QA reports in support of
                        the CMC section of the Phase I IND filing for
                        Angiostatin targeted for "...".





                                    6 of 27
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                                   APPENDIX 1



PROGRAM ASSUMPTIONS

Program assumptions are listed to provide a framework by which the Program may
proceed. If these assumptions prove to be incorrect, then alternative approaches
will need to be considered to achieve the stated deliverables.

1.    The Angiostatin process will require "..." for fermentation and "..." for
      recovery and purification (per "..." process).

2.    All technology transfer performs as represented by EntreMed.

3.    For Angiostatin, "..." will be sufficient to ensure process operation and
      reproducibility.

4.    Price and timelines assume "...".

5.    At large-scale, "...". Starting on "...".

6.    Angiostatin delivery dates are of critical importance to EntreMed. The
      program will be managed to maximize the likelihood of achieving
      Angiostatin delivery on or before the required dates. Process development
      activities will continue "..." to support large-scale manufacturing and to
      optimize/improve the manufacturing process prior to transfer of the
      process to manufacturing. Continuing process development will be in
      parallel with manufacturing; any improvements in the manufacturing process
      that are discovered by this parallel development work will be incorporated
      into the manufacturing process when practicable within the constraints of
      a cGMP environment.



                                    7 of 27
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                                   APPENDIX 1


ANGIOSTATIN DEVELOPMENT ACTIVITIES

            PLAN OF ACTION

            The objective of this activity is to develop a scaleable and cGMP
            compatible process that yields Angiostatin of appropriate quality
            for toxicology studies and clinical trials.

            -     Attempt to reproduce and scale up a fermentation process for
                  Angiostatin with reference to the existing CBSI process for
                  Endostatin. Perform additional development work as necessary.

            -     Attempt to reproduce and scale up a recovery process for
                  Angiostatin with reference to the existing CBSI process for
                  Endostatin. Perform additional development work as necessary.

            -     Attempt to reproduce and scale up a purification process for
                  Angiostatin with reference to the existing CBSI process for
                  Endostatin. Perform additional development work as necessary.

            -     Transfer/Develop methods to assess identity, purity,
                  concentration and product-related contaminants.

            CBSI will conduct appropriate Process Development efforts to specify
            both fermentation and purification yields and control production of
            the various species of Angiostatin.

            These process development efforts include some or all activities
            described on the following pages.



                                    8 of 27
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                                   APPENDIX 1




<TABLE>
<CAPTION>
-------------------------------------------------------------------------------------------------------------------------------
                         FERMENTATION PD ACTIVITY                  ESTIMATED        ESTIMATED         ESTIMATED
                                                                    NO. OF           NO. OF           FTE-WEEKS
                                                                   PERSONS            WEEKS
-------------------------------------------------------------------------------------------------------------------------------
<S>                                                              <C>                 <C>               <C>
"..."                                                              "..."             "..."              "..."
-------------------------------------------------------------------------------------------------------------------------------
"..."                                                              "..."             "..."              "..."
-------------------------------------------------------------------------------------------------------------------------------
"..."                                                              "..."             "..."              "..."
-------------------------------------------------------------------------------------------------------------------------------
TOTAL FTE-WEEKS NEEDED                                                                                  "..."
-------------------------------------------------------------------------------------------------------------------------------
</TABLE>




                                    9 of 27
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                                   APPENDIX 1





<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------
PURIFICATION PD ACTIVITY                             ESTIMATED          ESTIMATED           ESTIMATED
                                                     NO. OF             NO. OF              TOTAL
                                                     PERSONS            WEEKS               FTE-WEEKS
--------------------------------------------------------------------------------------------------------------
<S>                                               <C>                   <C>                 <C>
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
TOTAL FTE-WEEKS NEEDED                                                                      "..."
--------------------------------------------------------------------------------------------------------------
</TABLE>


<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------
ANALYTICAL PD ACTIVITY                               ESTIMATED          ESTIMATED           ESTIMATED
                                                     NO. OF             NO. OF              TOTAL
                                                     PERSONS            WEEKS               FTE-WEEKS
--------------------------------------------------------------------------------------------------------------
<S>                                               <C>                 <C>                 <C>
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
TOTAL FTE-WEEKS NEEDED                                                                      "..."
--------------------------------------------------------------------------------------------------------------
</TABLE>


<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------
FORMULATION PD ACTIVITY                              ESTIMATED          ESTIMATED           ESTIMATED
                                                     NO. OF             NO. OF              TOTAL
                                                     PERSONS            WEEKS               FTE-WEEKS
--------------------------------------------------------------------------------------------------------------
<S>                                               <C>                 <C>                 <C>
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
"..."                                                "..."              "..."               "..."
--------------------------------------------------------------------------------------------------------------
TOTAL FTE-WEEKS NEEDED                                                                      "..."
--------------------------------------------------------------------------------------------------------------
</TABLE>
     FINANCIAL SUMMARY

     -    "..."





                                    10 of 27
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                  with the Securities and Exchange Commission]

                                   APPENDIX 1


ANGIOSTATIN MANUFACTURING RELATED ACTIVITIES

            TECHNOLOGY TRANSFER

            The objective of this activity is to transfer from EntreMed to CBSI
            existing methodology and process information to obtain a complete
            understanding of the process as it currently exists.

                TECHNOLOGY TRANSFER includes the following activities:

                  -     EntreMed will transfer existing methods and technical
                        information from the "..." and "..." regarding the
                        fermentation and purification processes and analytical
                        techniques for quantifying Angiostatin

                  -     CBSI will verify raw materials and purchase long lead
                        time materials

                  -     CBSI will verify equipment requirements and purchase
                        long lead time items, if any

                  -     CBSI will identify any facility or equipment engineering
                        issues related to large-scale manufacture

                  -     CBSI will outline the manufacturing plan that includes
                        identifying technical issues with the facility,
                        scheduling of the facility, and development of detailed
                        timelines for specific production activities, including
                        changeover

            Price

             "..."



                                    11 of 27
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1


CELL BANKING AND TESTING

The objective of this activity is to generate and test a cGMP Master Cell Bank
(MCB) from a research cell bank and generate and test a Manufacturer's Working
Cell Bank (MWCB) from the MCB.

a)    CBSI will receive vials of the "..." following confirmation of purity and
      non-host contamination by "...". "..." must be "..." prior to receipt of
      cells.

b)    CBSI will develop specifications for all raw materials based on
      information provided by EntreMed. CBSI will order and release raw
      materials according to CBSI Standard Operating Procedures.

c)    CBSI will generate batch records for the cell bank production activities.
      EntreMed will review and approve all batch records prior to cell bank
      production.

d)    CBSI will produce a "..." vial MCB and a "..." vial MWCB from a MCB vial.
      CBSI Quality Group will provide support for batch record review and
      approval, raw material release and environmental monitoring.

e)    CBSI will provide temporary storage for cell banks ("..." degreesC).
      Within "..." of completion of cell banking activities, at least "..." of
      the cell bank will be transferred for storage to a designated third party
      approved by EntreMed.

f)    CBSI will perform the following tests on samples from the MCB and MWCB.
      CBSI and EntreMed will agree to suitable acceptance criteria for these
      tests:
              -    "..." ("...")
              -    "..." ("...")
              -    "..." ("...")

g)    CBSI will submit samples of the MCB and MWCB to "..." to perform the
      following. CBSI and EntreMed will agree to suitable acceptance criteria
      for these tests:
              -    "..." ("...")
              -    "..." ("...")

h)    CBSI will provide EntreMed with copies of the completed and approved batch
      records. CBSI will retain the originals in its archives.

i)    "..." testing of the MCB and MWCB is not included in the scope of this
      proposal.

j)    EntreMed is responsible for ensuring that the cell line supplied is
      suitable for the intended use.

Price
 "..."

            PRE-PRODUCTION ACTIVITIES

                                    12 of 27
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                                   APPENDIX 1



            The objective of this activity is for CBSI to perform the following
            activities in preparation for cGMP manufacturing:

                  -     Develop and finalize process flow diagrams

                  -     Complete engineering for processes

                  -     Prepare specifications

                  -     Test and release all raw materials

                  -     Procure and release all necessary supplies

                  -     Complete and qualify any necessary equipment
                        modifications

                  -     Prepare a detailed list of specifications, test methods,
                        SOPs, protocols and manufacturing procedures

                  -     Develop manufacturing procedures for implementation into
                        the CBSI Batch Record/Manufacturing Execution System

                  -     Set up to perform small scale runs, large scale
                        demonstration runs, toxicology runs and large scale cGMP
                        runs

            Price

            "..."(4)

            "..."





-----------------------------

            (4) "..."



                                    13 of 27
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                                   APPENDIX 1


            LARGE SCALE "..." DEMONSTRATION RUNS

                  -     "..." demonstration runs and subsequent purification
                        will be performed according to the procedures developed
                        including any change in methods determined to be useful
                        following "..." runs.

                  -     Additional "..." demonstration runs may be needed if
                        unforeseen scale-up issues arise ("...").

                  -     Records for this stage of the process will be maintained
                        using DRAFT cGMP documents (batch records and
                        formulation records).

                  -     Analytical assays will be preformed to verify product
                        identity and quality on material from these
                        demonstration runs using appropriate assays.

                  -     Specific goals for yield and purity will be mutually
                        agreed upon between EntreMed and CBSI based on early
                        development results, clinical needs and project
                        timelines.

                  The "..." scale activities will be performed in CBSI's large
                  scale manufacturing area. Each manufacturing run is expected
                  to require one week in the large-scale fermentation area and
                  one-week in the large scale purification area. Any material
                  produced during demonstration runs can be used for
                  formulation, stability and other non-clinical activities.

                  Price

                   "..."

            IT IS ASSUMED THAT "..." DEMONSTRATION RUNS WILL BE SUFFICIENT TO
            ENSURE PROCESS OPERATION AND REPRODUCIBILITY.

            MILESTONE: AFTER COMPLETION OF DEMONSTRATION RUNS, CBSI AND ENTREMED
            WILL DETERMINE THAT USEABLE ANGIOSTATIN CAN BE PRODUCED AT LARGE
            SCALE BASED ON THE REVIEW OF DATA.

            IF THE MILESTONE IS NOT ACHIEVED AFTER "..." DEMONSTRATION RUNS, THE
            PARTIES AGREE TO MODIFY THE SCOPE TO ACCOMMODATE ADDITIONAL
            DEVELOPMENT WORK AND DEMONSTRATION RUNS TO ACHIEVE THE MILESTONE.
            THE COST FOR THE ADDITIONAL DEMONSTRATION RUNS IS "...".




                                    14 of 27
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     Confidential Treatment Request, which the Company has filed separately
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                                   APPENDIX 1



            ASSAY QUALIFICATION

            The objective of this activity is to perform qualification of assays
            to assess the performance capability of the assays used in support
            of cGMP manufacturing and stability studies.

            EntreMed and CBSI will jointly determine the specific assays to be
            used for in-process control and Angiostatin release testing. The
            types of assays listed below will assess the identity, purity,
            strength and homogeneity of Angiostatin. The specific testing
            regimen will depend on the inherent properties of Angiostatin.

            This table lists the assays that may be employed for
            characterization, in-process control and release testing of
            Angiostatin.

<TABLE>
<CAPTION>
-----------------------------------------------------------------------------------------
                 METHOD                                     COST FOR QUALIFICATION
-----------------------------------------------------------------------------------------
<S>                                                         <C>
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
                  "..."                                             "..."
-----------------------------------------------------------------------------------------
</TABLE>


            Price

            "..."

            "..."





                                    15 of 27
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                                   APPENDIX 1



            cGMP STABILITY STUDIES

            The objective of this activity is to perform studies on clinical
            material produced in cGMP runs. Activities include:

            -     Evaluate final product configuration for stability in real
                  time conditions at anticipated storage temperatures

            -     Perform studies that at least cover the duration of the
                  clinical trial


            The following table/schedule illustrates a clinical trial lasting
            "..." with expected storage at "...":

<TABLE>
<CAPTION>
-------------------------------------------------------------------------------------------------------
                 T=0        T=1m            T=2m           T=3m           T=6m           T=9m
-------------------------------------------------------------------------------------------------------
<S>             <C>         <C>             <C>            <C>            <C>            <C>
"..." degrees C  "..."      "..."           "..."          "..."          "..."          "..."
-------------------------------------------------------------------------------------------------------
"..." degrees C  "..."      "..."           "..."          "..."          "..."          "..."
-------------------------------------------------------------------------------------------------------
</TABLE>


            CBSI will prepare a report describing the stability data for
            Angiostatin.

            The duration of cGMP stability studies depends on study design and
            duration of clinical trial.

            Price

            "..."

            "..."




                                    16 of 27
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                                   APPENDIX 1



            REGULATORY SUPPORT SERVICES

            The objective of this activity is to support the regulatory aspects
            of manufacturing Angiostatin at the CBSI facility.

            The Regulatory support segment includes the following activities:

                  -     Prepare site documents

                  -     Prepare scale-up/development and other reports

                  -     Write the CMC sections for Phase I IND filing

                  -     Respond to any questions related to manufacturing raised
                        by regulatory authorities

                  -     Host any inspections


            Price

            "..."

            "...":      "..."

            "..."



                                    17 of 27
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1


            PROGRAM MANAGEMENT

            CBSI takes a Program Team approach to managing all manufacturing
            projects. The Program Team would consist of a CBSI Program Manager,
            a representative from EntreMed and CBSI representatives from process
            development, quality and manufacturing. The Program Team would meet
            weekly via teleconference or in person.

            The Executive Committee will meet on a monthly basis (or as
            required) to review Program progress, review budgetary progress and
            address any outstanding issues.

            The Program Manager is responsible for coordination of all technical
            aspects of the Program, including monitoring financial and temporal
            progress of the Program and submitting periodic reports.

            CBSI will provide a Program Manager for the duration of the project.

            Price

            "..."




            FILL/FINISH OF TOXICOLOGY MATERIAL

            The objective of this activity is to vial Angiostatin for toxicology
            studies.

                  -     The fill concentration for Angiostatin toxicology
                        material will be "..." in a formulation to be mutually
                        determined.

                  -     CBSI will perform "..." vial fills in "..." vials ("..."
                        per vial).


            Price

             "..."










                                    18 of 27
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



QA RELEASE TESTING OF VIALED CLINICAL MATERIAL

            The objective of this activity is to provide QC testing of vialed
            Angiostatin for use in human clinical studies.

                  -     Receive vialed Angiostatin from "...".

                  -     Test vialed Angiostatin per Item Specifications to be
                        determined. Testing to be performed by CBSI QC staff.

                  -     Provide certificate of analysis, released by QA, for
                        vialed Angiostatin.

            Price

            The price for this phase of the Program is "...".

            "..."


  SAMPLING OF LARGE SCALE DEMONSTRATION RUNS FOR DIAGNOSTIC PURPOSES

            The objective of this activity is to allow diagnostic assessment of
            the large scale production process for Angiostatin.

                  -     Draw samples at appropriate process points during large
                        scale demonstration runs for diagnostic assessment of
                        Angiostatin activity
                  -     Ship samples to EntreMed for diagnostic assessment

            Price

            The price for sampling and shipping samples is "...".  "...".




                                    19 of 27
<PAGE>   31
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1


FINANCIAL SUMMARY FOR "..." COMPONENTS OF ANGIOSTATIN MANUFACTURING RELATED
ACTIVITIES



<TABLE>
<CAPTION>
------------------------------------------------------------------------------------------------------------
                           ANGIOSTATIN MANUFACTURING RELATED
                                        ACTIVITIES                                        "..."
------------------------------------------------------------------------------------------------------------

<S>                                                                                       <C>
Technology Transfer                                                                                   "..."
------------------------------------------------------------------------------------------------------------

Cell Banking and Testing                                                                              "..."
------------------------------------------------------------------------------------------------------------

Pre-Production Activities                                                                             "..."
------------------------------------------------------------------------------------------------------------

Large Scale "..." Demonstration Runs                                                                  "..."
------------------------------------------------------------------------------------------------------------

Assay Qualification                                                                                   "..."
------------------------------------------------------------------------------------------------------------

cGMP Stability Studies (for estimated "...")                                                          "..."
------------------------------------------------------------------------------------------------------------

Regulatory Support                                                                                    "..."
------------------------------------------------------------------------------------------------------------

Project Management                                                                                    "..."
------------------------------------------------------------------------------------------------------------

Fill/Finish of Toxicology Material (for estimated "...")                                              "..."
------------------------------------------------------------------------------------------------------------

TOTAL                                                                                                 "..."
------------------------------------------------------------------------------------------------------------
</TABLE>



--------------------------------------------------------------------------------
"...".
--------------------------------------------------------------------------------





                                    20 of 27
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



      ANGIOSTATIN LARGE SCALE PRODUCTION OF "..."

      MILESTONE: BEFORE INITIATING TOXICOLOGY MANUFACTURING, CBSI AND ENTREMED
      WILL DETERMINE THAT USEABLE ANGIOSTATIN CAN BE PRODUCED AT LARGE SCALE
      BASED ON THE REVIEW OF DATA FROM THE DEMONSTRATION RUNS.

            TOXICOLOGY MATERIAL MANUFACTURING

            The objective of this activity is to produce material for use in
            toxicology studies and to perform demonstration runs on the
            fermentation process.

            The "..."  MWCB will be used for manufacture of toxicology material.

            Draft cGMP documentation as prepared during pre-production
            activities will be used during production of toxicology material.

            The Quality department will release raw materials used for the
            manufacture of toxicology material.

            CBSI will perform the appropriate number of "..." fermentation runs
            in series with subsequent purification to produce approximately
            "..." of Angiostatin for toxicology studies. CBSI will use its best
            judgement to establish a manufacturing strategy in consultation with
            EntreMed.

            The Analytical Development Group will perform preliminary analysis
            of samples using appropriate assays.

            The Quality Assurance Group will not perform a formal review of
            documentation.

            Toxicology material will be released to EntreMed based on the
            Quality Control (QC) criteria listed below:

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."


            CBSI will provide EntreMed with copies of the documentation used
            during toxicology production. CBSI will retain the originals in its
            archives.

                                    21 of 27
<PAGE>   33
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1

            Estimated Price

            See "FINANCIAL SUMMARY FOR ANGIOSTATIN MANUFACTURING" on pages 26-27
            for details

            Note:  If EntreMed requests "...".




                                    22 of 27
<PAGE>   34
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     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



            CLINICAL TRIAL MATERIAL MANUFACTURING

            The objective of this activity is to produce cGMP quality material
            for use in Phase I clinical trials.

            The "..." MWCB will be used for cGMP manufacture of clinical
            material.

            cGMP documentation as prepared during pre-production activities and
            modified during demonstration runs will be adhered to and
            manufacturing will be performed under Quality Assurance oversight as
            described in the Quality Function section.

            CBSI will perform the appropriate number of "..." fermentation runs
            in series with subsequent purification to produce "..." of
            Angiostatin for clinical trials. CBSI will use its best judgement to
            establish a manufacturing strategy in consultation with EntreMed.

            Release criteria for clinical material is to be developed and agreed
            to before clinical trial material manufacturing.


            Note: When manufacturing clinical material, CBSI will follow current
            Good Manufacturing Practices. By testing this material against
            analytical specifications, CBSI will demonstrate this material meets
            specifications for purity and contamination levels. CBSI does not
            warrant that the material produced under cGMP will be biologically
            active. Clinical studies will be used to determine if the material
            is efficacious.


            Analytical methods to verify substance identity and quality will be
            performed by the QC department.

            CBSI will provide EntreMed with copies of the completed and approved
            batch records. All records will be in pre-approved cGMP documents
            subject to full QA review. CBSI will retain the originals in its
            archives.

            Estimated Price

            See "FINANCIAL SUMMARY FOR ANGIOSTATIN MANUFACTURING" on pages 26-27
            for details

            Note:  If EntreMed requests "...".



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            [ "..." indicates material has been omitted pursuant to a
     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



            QUALITY FUNCTION

            The objective of this activity is to provide Quality Control and
            Quality Assurance support for cGMP manufacturing activities.
            Activities include:

            -     Provide support to ensure cGMP compliance of clinical material
                  production.

            -     Issue and maintain controlled documents such as item
                  specifications and batch records.

            -     Prepare certificates of analysis.

            -     Perform IPC and Product testing according to approved test
                  methods and specifications.

            -     Characterize reference standard

            -     Compare Angiostatin to reference standard.

            -     Review and approve completed production and environmental
                  control records.

            -     Select, qualify and/or audit vendors, if necessary


            IPC and Product release tests may include the following methods:

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."

                  -     "..."


            Estimated Labor

            "...".

            Estimated Price

            See "FINANCIAL SUMMARY FOR ANGIOSTATIN MANUFACTURING" on pages 26-27
            for details.



                                    24 of 27
<PAGE>   36
            [ "..." indicates material has been omitted pursuant to a
     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1


FINANCIAL SUMMARY FOR ANGIOSTATIN MANUFACTURING


Table 1
<TABLE>
<CAPTION>
----------------------------------------------------------------------------------------------------------------------------
                                             Assumptions                                                   Price per run
----------------------------------------------------------------------------------------------------------------------------
<S>                                                                                                      <C>
1.     If the process requires:                                                                                "..."
       -     "..." for fermentation
       -     "..." for recovery and purification
----------------------------------------------------------------------------------------------------------------------------
2.     If the process requires:                                                                                "..."
       -     "..." for fermentation
       -     MORE THAN "..." AND LESS THAN OR EQUAL TO "..." for recovery and purification
----------------------------------------------------------------------------------------------------------------------------
3.     If the process requires:                                                                                "..."
       -     LESS THAN "..." for fermentation and/or
       -     LESS THAN "..." for recovery and purification
----------------------------------------------------------------------------------------------------------------------------
4.   If the process requires processing times greater than those indicated in 2. (above), then
      Parties agree that the process is economically unviable and agree to discuss how best to proceed.
----------------------------------------------------------------------------------------------------------------------------
</TABLE>






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<PAGE>   37
            [ "..." indicates material has been omitted pursuant to a
     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



The price for this section will be based on "...".  "...".

Table 2
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------------------
<S>                                          <C>                      <C>                           <C>
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
           "..."                              "..."                       "..."                      "..."
--------------------------------------------------------------------------------------------------------------------------
</TABLE>


Note:  If EntreMed requests "...".


"...".

--------------------------------------------------------------------------------
"...".
--------------------------------------------------------------------------------



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<PAGE>   38
            [ "..." indicates material has been omitted pursuant to a
     Confidential Treatment Request, which the Company has filed separately
                  with the Securities and Exchange Commission]

                                   APPENDIX 1



ESTIMATED PAYMENT SCHEDULE




<TABLE>
<CAPTION>
----------------------------------------------------------------------------------------------------------------------
                        FINANCIAL SUMMARY                                                  PAYMENT SCHEDULE
----------------------------------------------------------------------------------------------------------------------
<S>                                                                                  <C>
Angiostatin Process Development Activities                                                     "..."
----------------------------------------------------------------------------------------------------------------------

"..." Components of Angiostatin Manufacturing-Related Activites                                "..."
----------------------------------------------------------------------------------------------------------------------

Angiostatin Manufacturing                                                                      "..."
----------------------------------------------------------------------------------------------------------------------
</TABLE>




ACCEPTANCE SIGNATURE


Signature below indicates acceptance of this scope of work.


COVANCE BIOTECHNOLOGY SERVICES INC.               ENTREMED, INC.



By: /s/  JOHN R. BROWN                            By: /s/ JOHN W. HOLADAY
   -------------------                               --------------------

Date: July 7, 1999                                Date: July 7, 1999
      ----------------------                            --------------------



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