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                                                                   Exhibit 10.46

                                [LOGO ENTREMED]

                             CONFIDENTIAL AGREEMENT
                               AND MUTUAL RELEASE

This Confidential Separation Agreement and General Release ("Agreement") is
entered into September 18, 2002 (the Effective Date) between EntreMed, Inc, a
Delaware corporation ("The Company") and Edward R. Gubish, Ph.D. ("you"). The
purpose of this Agreement is to set out the terms and conditions surrounding
your termination of employment from the Company.

1.   This is to confirm that your employment with the Company will cease,
     effective October 15, 2002 ("the termination date").

2.   The Company agrees to pay you, as severance, twelve (12) months of salary.
     You will receive separation payments of your regular salary less
     appropriate withholdings. These payments will be sent to you by mail or
     will be paid to you via direct deposit, if you so choose, on the Company's
     normal paydays for employees through October 15, 2003. You are not
     entitled to receive any additional compensation and you will not accrue
     additional separation or other pay during your inactive employment. In the
     event you commence employment elsewhere you will receive a lump sum
     corresponding to the portion of your salary payments that would have been
     paid out to you.

3.   Vacation accrual will cease on October 15, 2002. Under the Company's
     vacation policy you will receive a lump sum payment for any accrued and
     unused vacation days less appropriate withholding, on the normal payday
     after your active employment ends.

4.   You will receive stock option grants and/or bonuses for 2001, should they
     be granted by the EntreMed Board of Directors. You will receive stock
     option grants and/or bonuses for 2002, should they be granted by the
     EntreMed Board of Directors. The number of stock options granted to you for
     2002 is 40,000 options. All granted options that are unvested will be
     vested on the Effective Date of this agreement. You will be able to
     exercise any vested option held by you after leaving the Company through
     the original expiration date of the option (generally, 10 years from the
     original grant date). Your current options (including those granted in
     2002) total 672,001 and are listed on the attached schedule.
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5.   The Company shall have no other financial obligations to you under any
     compensation or benefit plan, program or policy, and your participation in
     the Company compensation and benefit plans, programs and policies shall
     cease as of the date of your termination, except that you shall have such
     right to continued group health plan coverage as is provided under COBRA.
     COBRA payments will be paid for 12 months after your termination date of
     October 15, 2002 or until you acquire a new position with a new employer.

6.   In exchange for the consideration described in this document, you agree to
     release and forever discharge the Company, its subsidiaries and affiliates
     and their parent organizations, predecessors, successors, officers,
     directors, employees, agents, attorneys, associates and employee benefit
     plans from all claims, demands or causes of action arising out of facts or
     occurrences prior to the date of this Agreement, whether known or unknown
     to you.

     The Company, for itself, its officers, directors, employees, agents and
     successors and assigns releases and forever discharges you and your heirs,
     successors and assigns from all claims, demands or causes of action arising
     out of facts or occurrences prior to the date of this Agreement, whether
     known or unknown, except to the extent that any such claim, demand or cause
     of action is based on your actions which do not meet the required standard
     for indemnification set forth in the Delaware Corporation Law (whether such
     actions were taken in your capacity as an officer or employee). In this
     connection it is understood that you shall be entitled to reimbursement
     applicable to your action or inactions as an officer or employee of the
     Company under the terms of the current Directors and Officers Liability
     Insurance and the Company will indemnify you in this regard to the extent
     provided by its By-Laws consistent with Delaware Law.

7.   You and the Company agree that the release of claims set forth herein is
     intended to be broadly construed so as to resolve any pending and potential
     disputes between you and the Company that may exist up to the date of such
     Release, whether or not such disputes are known or unknown, including, but
     not limited to, claims based on express or implied contract; any action
     arising in tort, including, but not limited to libel, slander, defamation,
     intentional infliction of emotional distress, or negligence; any or all
     claims for wrongful discharge; and any and all claims based on the Age
     Discrimination in Employment Act (42 U.S.C. section 621), Title VII of the
     Civil Rights Act of 1964 as amended (42 U.S.C. section 2000e), the Civil
     Rights Acts of 1866 and 1871 (42 U.S.C. section 1981), the Employee
     Retirement Income Security Act (29 U.S.C. section 1001), the Family and
     Medical Leave Act (29 U.S.C. section 2601), the Americans with Disabilities
     Act (42 U.S.C. section 12,101), the Occupational Safety and Health Act
     (29 U.S.C. section 651), the Maryland Fair Employment Practices Act, and
     any other applicable federal, state or local law, regulation, ordinance, or
     order.

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     Notwithstanding anything to the contrary in this paragraph or in paragraph
     9, nothing in these paragraphs shall release or be construed to as
     releasing any claim, demand or cause of action arising under this
     Agreement.

8.   In further consideration for the compensation and benefits herein, you
     agree strictly to maintain the confidentiality of this Agreement and not to
     disclose its existence or its terms to anyone other than your spouse,
     attorney and any tax advisors except as may be required by law or legal
     process. The Company will similarly maintain the confidentiality of this
     Agreement and not disclose its existence or its terms to anyone other than
     to its professional advisors, to employee or agents who have a need to know
     and as may be required by law or legal process.

9.   In connection with litigation or proceedings or anticipated proceedings,
     before a court, arbitrator, administrative agency or other tribunal, should
     you be asked by the Company to testify as a witness or to provide
     information to the Company's counsel concerning matters you were involved
     in during the course of your employment with the Company, you agree to
     cooperate fully with the Company's counsel. You agree to make yourself
     available to such counsel to discuss your information and to review your
     testimony reasonably in advance of such litigation or proceedings and to
     make yourself available to testify at depositions or trial as required or
     requested by the Company. You will be reimbursed for travel expenses and
     statutorily-mandated witness fees; however, you agree that you will not be
     paid in connection with your testimony, appearance or participation
     pursuant to this paragraph in such litigation or proceedings.
     Notwithstanding the foregoing, in the event your appearance or testimony
     causes you a loss of regular employment earnings for said appearance or
     testimony, the Company will reimburse you for such loss of earnings.

10.  This Agreement is specifically conditioned on your continuing to abide by
     all the terms and conditions of this Agreement and the terms and conditions
     set forth in the Company's standard confidentiality agreement, including,
     but not limited to, your agreement not to disclose any information to any
     third party relating to the Company's research, finances, product
     development, manufacturing, business/commercial development, sales and
     marketing strategies and activities. You agree not to make any false,
     disparaging or derogatory statements in public or private regarding the
     Company or any of its officers, directors, employees, agents or
     representatives or the Company's business affairs or financial condition.
     The Company agrees that neither it nor any of its officers, directors or
     agents will make any false, disparaging or derogatory statements in public
     or private in connection with or concerning your service to the Company or
     your separation therefrom. In addition, in regard to any inquiries made by
     third parties with respect to your employment


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     at the Company, the Company will confirm only your dates of employment, job
     title and salary and you and the Company shall mutually agree upon any
     public statements regarding your separation from the Company before its
     issuance. Further, for a period of nine (9) months after termination of
     your active employment with the Company, you agree not to, as an
     individual, principal, agent, employee, consultant or otherwise, directly
     or indirectly in the United States render any services to Celgene
     Corporation.

11.  Moreover, for a period of nine (9) months after the termination of your
     employment (October 15, 2002) with the Company, you agree not to take any
     action to assist your successor employer or any other entity in recruiting
     or hiring any other employee who had worked for the Company during any of
     the time period when you worked for the Company. This includes (a)
     identifying to such successor employer or its agents or such other entity,
     the person or persons who have special knowledge concerning the Company's
     inventions, processes, methods or confidential affairs; or (b) commenting
     to your successor employer or its agents or such other entity about the
     quantity of work, quality of work, special knowledge or personal
     characteristics of any person who is still employed at the Company. You
     also agree that you will not provide such information to a prospective
     employer during interviews preceding possible employment. If you breach or
     challenge the enforceability of this Agreement in a court of law before an
     administrative agency, you acknowledge that you will reimburse the Company
     for any monetary consideration previously received by you under this
     Agreement. If the Company breaches this Agreement, the Company acknowledges
     that it may be liable for monetary damages you incurred as a result and/or
     you may be entitled to equitable relief. You and the Company agree that the
     prevailing party in any proceeding (judicial or administrative) to enforce
     this Agreement will be entitled to an award of reasonable attorneys' fees
     and costs actually incurred.

12.  You expressly agree that you will not apply for reinstatement or
     reemployment with the Company, although this obligation will not be
     applicable to any entity which may acquire all of the assets of the Company
     or be the surviving entity following a merger with the Company.

13.  You shall immediately return to the Company all notes, reports, plans,
     keys, security cards and/or identification cards, customer lists, product
     information and other documents and property that were created, developed,
     generated or received by you during your employment or that are the
     property of the Company, whether or not such items are confidential to the
     Company. It is understood that this obligation does not apply to items that
     are clearly intended to be retained by you after separation from the
     Company, i.e., pay stubs. It is also understood that this obligation does
     not apply to your laptop computer.

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14.  This agreement shall not be construed as an admission by the Company of
     any wrongdoing or any violation of federal, state or local law, and the
     Company specifically disclaims any wrongdoing against, or liability to you.

Ed Gubish acknowledges and agrees as follows:

15.  I have read and understand this Agreement in its entirety;

     a.   I have been advised by the Company to consult with an attorney before
          signing this Agreement and this paragraph constitutes such advice in
          writing;

     b.   I have been advised that I have 45 days from the date of this
          agreement to sign and return the agreement to EntreMed, Inc. in order
          for this agreement to take effect. I also understand that I have
          7 days from the date of signature to revoke the signed agreement; and

     c.   I have entered this Agreement knowingly and voluntarily, without
          duress or reservation of any kind, and after having given the matter
          full and careful consideration.

16.  This Agreement contains the entire agreement between you and the Company
     concerning your separation from employment.

17.  This Agreement shall be construed and enforced under Maryland law without
     regard to conflict of law principles, to the extent not governed by
     federal law.

18.  In the event any portion of this Agreement is deemed to be invalid or
     unenforceable, that portion will be deemed to be omitted and the remainder
     of this Agreement will remain in full force and effect.

            PLEASE READ CAREFULLY. THIS AGREEMENT INCLUDES A RELEASE
                    OF ALL CLAIMS, WHETHER KNOWN OR UNKNOWN,
                YOU MAY HAVE IN CONNECTION WITH YOUR EMPLOYMENT
                                WITH THE COMPANY.

Dated: September 18, 2002


                                                    /s/ Edward R. Gubish, Ph.D.
                                                    ----------------------------
                                                        Edward R. Gubish, Ph.D.

/s/ John W. Holaday
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By: John W. Holaday
Chairman and CEO
EntreMed, Inc.


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