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Separation Agreement and General Release - Ligand Pharmaceuticals Inc. and Thomas H. Silberg

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                    SEPARATION AGREEMENT AND GENERAL RELEASE

     THIS SEPARATION AGREEMENT AND GENERAL RELEASE (hereinafter "AGREEMENT") is
made and entered into by and between Thomas H. Silberg (hereinafter "SILBERG")
and Ligand Pharmaceuticals Incorporated (hereinafter "LIGAND"), and inures to
the benefit of each of LIGAND's current, former and future parents,
subsidiaries, related entities, employee benefit plans and their fiduciaries,
predecessors, successors, officers, directors, shareholders, agents, employees
and assigns.

                                    RECITALS

     A. SILBERG was for a period of time an employee of LIGAND, most recently as
its Executive Vice President and Chief Operating Officer.

     B. SILBERG has been a corporate officer of LIGAND.

     C. SILBERG's employment with LIGAND ended effective May 13, 2003.

     D. At the time of separation, SILBERG had vested options to purchase shares
of LIGAND common stock as follows: 18,333 options at $10.6800/option; 21,875
options at $15.2400/option; and 101,563 options at $16.3750/option.

     E. On or about October 26, 2000, LIGAND loaned SILBERG the principal sum of
$150,000 pursuant to a written Promissory Note ("Note"). As of May 13, 2003, the
principal balance remaining due on SILBERG's Note was $73,700.00.

     F. SILBERG and LIGAND wish permanently to resolve any and all disputes
arising out of SILBERG's employment with LIGAND or the cessation of that
employment.

     NOW, THEREFORE, for and in consideration of the execution of this AGREEMENT
and the mutual covenants contained in the following paragraphs, LIGAND and
SILBERG agree as follows:

     1. INCORPORATION OF RECITALS. The Recitals and identification of the
parties to, and beneficiaries of, this AGREEMENT are incorporated by references
as though fully set forth herein.

     2. NO ADMISSION OF LIABILITY. The parties agree that this AGREEMENT, and
performance of the acts required by it, does not constitute an admission of
liability, culpability, negligence or wrongdoing on the part of anyone, and will
not be construed for any purpose as an admission of liability, culpability,
negligence or wrongdoing by any party and/or by any party's current, former or
fixture parents, subsidiaries, related entities, predecessors, successors,
officers, directors, shareholders, agents, employees and assigns.

     3. CESSATION OF EMPLOYMENT. SILBERG's employment with LIGAND terminated May
13, 2003. SILBERG hereby acknowledges his resignation from his employment and
all officer positions within LIGAND.


<PAGE>

     4. WAGES AND VACATION TIME PAID. SILBERG acknowledges that he has been paid
for all of his wages and his accrued and unused vacation time through May 13,
2003.

     5. SEVERANCE. In consideration of the general release and other covenants
given by SILBERG pursuant to this AGREEMENT, LIGAND agrees that after the
Effective Date of this AGREEMENT (as defined in paragraph 30 hereof), it will
commence paying to SILBERG severance payments. The severance payments shall
equal, in the aggregate, the gross sum of *** (representing *** months' salary,
or *** less *** to be paid on the Note as described in paragraph 6 below), less
applicable withholding taxes. Severance payments shall commence on the first
regular payroll date following the Effective Date, and shall continue until ***
equal payments of *** have been made less applicable withholding taxes.

     6. NOTE. As of the Separation Date, the outstanding balance on the Note was
$73,700.00. In consideration of the general release and other covenants given by
SILBERG pursuant to this AGREEMENT, LIGAND agrees to credit SILBERG with ***
pursuant to the terms of the Note, which leaves a remaining balance, including
taxes, of ***. This sum of *** is being repaid by SILBERG through deductions
from his *** severance payments. The severance amounts referred to in paragraph
5 above reflect SILBERG's repayment of the aggregate sum of ***. Upon payment of
the severance payments described in paragraph 5 above, the Note will be paid in
full and will be cancelled.

     7. OUTPLACEMENT SERVICES. LIGAND shall pay SILBERG on the first business
day following the expiration of the 7-day revocation period set forth in
paragraph 29 the following: ***, less required withholding taxes, in lieu of
outplacement services.

     8. PRIOR AGREEMENTS SUPERSEDED. With the exception of the Proprietary
Information and Inventions Agreement signed by SILBERG on January 17, 2000, all
prior agreements or understandings between the parties are superseded and are of
no further force and effect. SILBERG understands and agrees that all of the
terms of the Proprietary Information and Inventions Agreement remain in force
and he agrees to maintain the confidentiality of non-public information
concerning LIGAND.

     9. REFERENCE REQUESTS. LIGAND agrees that if it is contacted by prospective
employers of SILBERG, LIGAND will release information concerning the dates of
SILBERG's employment and the last position held, and will advise prospective
employers of SILBERG that LIGAND's company policy is to release only such
information.

     10. CONTINUATION OF HEALTH BENEFITS. SILBERG acknowledges that he has been
provided with written materials which describe his rights to continue his and
his dependents' participation in LIGAND's group dental and vision insurance
plans pursuant to the provisions of the Consolidated Omnibus Budget
Reconciliation Act ("COBRA"). If SILBERG timely elects to continue his and his
dependents' participation in such plans pursuant to the provisions of COBRA,
LIGAND will pay the premiums on behalf of SILBERG and his participating




***Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.


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<PAGE>

dependents through ***. Continued participation after *** shall be at SILBERG's
expense. Nothing herein shall limit the right of LIGAND to change the provider
and/or the terms of its group health insurance plan at any time hereafter.

     11. EXERCISE OF VESTED STOCK OPTIONS. SILBERG understands and agrees that
he has ninety (90) days from the date on which his employment with LIGAND
terminated (i.e., 90 days from May 13, 2003) in which to advise LIGAND in
writing of his election to exercise all or a portion of his vested stock
options, to tender to LIGAND a cashier's check in an amount equal to the
appropriate exercise amount and all applicable withholding taxes, and to provide
to LIGAND all executed subscription documents as required by LIGAND pursuant to
the 2002 Ligand Stock Incentive Plan.

     12. GENERAL RELEASE. (a) SILBERG for himself, his heirs, executors,
administrators, assigns and successors, fully and forever releases and
discharges LIGAND and each of its current, former and future parents,
subsidiaries, related entities, employee benefit plans and their fiduciaries,
predecessors, successors, officers, directors, shareholders, agents, employees
and assigns (collectively, "Ligand Releasees"), with respect to any and all
claims, liabilities and causes of action, of every nature, kind and description,
in law, equity or otherwise, which have arisen, occurred or existed at any time
prior to the signing of this AGREEMENT, including, without limitation, any and
all claims, liabilities and causes of action arising out of or relating to
SILBERG's employment with LIGAND or the cessation of that employment.

     (b) LIGAND for itself, its affiliates, assigns and successors, fully and
forever releases and discharges SILBERG and each of his heirs, executors,
administrators, assigns and successors (collectively, "Silberg Releasees"), with
respect to any and all claims, liabilities and causes of action, of every
nature, kind and description, in law, equity or otherwise, which have arisen,
occurred or existed at any time prior to the signing of this AGREEMENT,
including, without limitation, any and all claims, liabilities and causes of
action arising out of or relating to SILBERG's employment with LIGAND or the
cessation of that employment.

     13. KNOWING WAIVER OF EMPLOYMENT-RELATED CLAIMS. SILBERG understands and
agrees that, with the exception of potential employment-related claims
identified below, he is waiving any and all rights he may have had, now has, or
in the future may have, to pursue against any of the Ligand Releasees any and
all remedies available to him under any employment-related causes of action,
including without limitation, claims of wrongful discharge, breach of contract,
breach of the covenant of good faith and fair dealing, fraud, violation of
public policy, defamation, discrimination, personal injury, physical injury,
emotional distress, claims for severance (except as provided for in this
AGREEMENT), claims for benefits or perquisites of employment (including stock
options), claims under Title VII of the Civil Rights Act of 1964, as amended,
the Age Discrimination in Employment Act, the Americans With Disabilities Act,
the Federal Rehabilitation Act, the Family and Medical Leave Act, the California
Fair Employment and Housing Act, the California Family Rights Act, the Equal Pay
Act of 1963, the provisions of the California Labor Code and any other federal,
state or local laws and regulations relating to employment, conditions of
employment (including wage and hour laws) and/or employment discrimination.
Claims not covered by the release provisions of this AGREEMENT are (i) claims
for unemployment insurance benefits, and (ii) claims under the California
Workers' Compensation Act.




***Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.


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<PAGE>

     14. WAIVER OF CIVIL CODE SS.1542. Each party expressly waives any and all
rights and benefits conferred upon it by Section 1542 of the Civil Code of the
State of California, which states as follows:

                  "A general release does not extend to claims which the
                  creditor does not know or suspect to exist in his favor at the
                  time of executing the release, which if known by him must have
                  materially affected his settlement with the debtor."

Each party expressly agrees and understands that the Release given by it
pursuant to this AGREEMENT applies to all unknown, unsuspected and unanticipated
claims, liabilities and causes of action which he may have against the other
party, any of the Ligand Releasees or Silberg Releasees.

     15. SEVERABILITY OF RELEASE PROVISIONS. Each party agrees that if any
provision of the release given by it under this AGREEMENT is found to be
unenforceable, it will not affect the enforceability of the remaining provisions
and the courts may enforce all remaining provisions to the extent permitted by
law.

     16. PROMISE TO REFRAIN FROM SUIT OR ADMINISTRATIVE ACTION. Each party
promises and agrees that it will never sue the other party, any of the Ligand
Releasees or Silberg Releasees, or otherwise institute or participate in any
legal or administrative proceedings against the foregoing entities, with respect
to any claim covered by the release provisions of this AGREEMENT, including but
not limited to claims arising out of SILBERG's employment with LIGAND or the
termination of that employment, unless it is compelled by legal process to do
so.

     17. PROMISE TO REFRAIN FROM ASSISTING IN SUIT OR ADMINISTRATIVE ACTION.
Each party promises and agrees that it shall not advocate or incite the
institution of, or assist or participate in, any suit, complaint, charge or
administrative proceeding by any other person against the other party hereto,
any of the LigandReleasees or Silberg Releasees, unless compelled by legal
process to do so.

     18. CONFIDENTIALITY OF SETTLEMENT. Each party promises and agrees that,
unless compelled by legal process, it will not disclose to others and will keep
confidential the terms of this settlement, including the amounts referred to in
this AGREEMENT, except that they may disclose this information to SILBERG's
spouse and to their attorneys, accountants and other professional advisors to
whom the disclosure is necessary to accomplish the purposes for which the party
has consulted such professional advisors. SILBERG expressly promises and agrees
that, unless compelled by legal process, he will not disclose to any present or
former employees of LIGAND the terms of this settlement. Notwithstanding the
foregoing, the parties acknowledge that this AGREEMENT is required to be filed
with the Securities and Exchange Commission, pursuant to its rules and
regulations. Confidential Treatment may be requested for certain portions, but
may not be granted as to all or part of such request.

     19. PROMISE TO MAINTAIN CONFIDENTIALITY OF LIGAND'S CONFIDENTIAL
INFORMATION. SILBERG acknowledges that due to the position he has occupied and
the responsibilities he has had at LIGAND, he has received confidential
information concerning LIGAND's products,


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<PAGE>

research and development, customers, sales, prices, contracts, and the like.
SILBERG hereby promises and agrees that, unless compelled by legal process, he
will not disclose to others and will keep confidential all information he has
received while employed by LIGAND concerning LIGAND's products and procedures,
its research and development, the identities of LIGAND's customers, LIGAND's
sales, LIGAND's prices, the terms of any of LIGAND's contracts with third
parties, and the like. SILBERG agrees that a violation by him of the foregoing
obligation to maintain the confidentiality of LIGAND's confidential information
will constitute a material breach of this AGREEMENT. SILBERG specifically
confirms that he will continue to comply with the terms of the Proprietary
Information and Inventions Agreement executed by him on January 17, 2000.

     20. NONSOLICITATION. SILBERG agrees that for a period of two (2) years from
the Effective Date of this AGREEMENT, he shall not, without the prior written
consent of the Company's Board of Directors, directly or indirectly solicit for
employment, employ in any capacity, or make an unsolicited recommendation to any
other person that it employ or solicit for employment any person who is or was,
at the time of SILBERG's separation, an officer, executive, employee, agent or
representative of the Company or of any affiliate of the Company.

     21. INTEGRATED AGREEMENT. The parties acknowledge and agree that no
promises or representations were made to them which do not appear written herein
and that this AGREEMENT contains the entire agreement of the parties on the
subject matter thereof. The parties further acknowledge and agree that parol
evidence shall not be required to interpret the intent of the parties.

     22. VOLUNTARY EXECUTION. The parties hereby acknowledge that they have read
and understand this AGREEMENT and that they sign this AGREEMENT voluntarily and
without coercion.

     23. WAIVER AMENDMENT AND MODIFICATION OF AGREEMENT. The parties agree that
no waiver, amendment or modification of any of the terms of this AGREEMENT shall
be effective unless in writing and signed by all parties affected by the waiver,
amendment or modification. No waiver of any term, condition or default of any
term of this AGREEMENT shall be construed as a waiver of any other term,
condition or default.

     24. REPRESENTATION BY COUNSEL. The parties acknowledge that they have had
the opportunity to be represented in negotiations for the preparation of this
AGREEMENT by counsel of their own choosing, and that they have entered into this
AGREEMENT voluntarily, without coercion, and based upon their own judgment and
not in reliance upon any representations or promises made by the other party or
parties or any attorneys, other than those contained within this AGREEMENT. The
parties further agree that if any of the facts or matters upon which they now
rely in making this AGREEMENT hereafter prove to be otherwise, this AGREEMENT
will nonetheless remain in full force and effect.

     25. CALIFORNIA LAW. The parties agree that this AGREEMENT and its terms
shall be construed under California law.


                                      -5-

<PAGE>

     26. DRAFTING. The parties agree that this AGREEMENT shall be construed
without regard to the drafter of the same and shall be construed as though each
party to this AGREEMENT participated equally in the preparation and drafting of
this AGREEMENT.

     27. COUNTERPARTS. This AGREEMENT may be signed in counterparts and said
counterparts shall be treated as though signed as one document.

     28. PERIOD TO CONSIDER TERMS OF AGREEMENT. SILBERG acknowledges that this
AGREEMENT was presented to him on June 20, 2003 and that he is entitled to have
21 days' time in which to consider the terms of this AGREEMENT. SILBERG
acknowledges that he has had the opportunity to obtain the advice and counsel
from the legal representative of his choice and that he executes this AGREEMENT
having had sufficient time within which to consider its terms. SILBERG
represents that if he executes this AGREEMENT before 21 days have elapsed, he
does so voluntarily and waives any remaining consideration period.

     29. REVOCATION OF AGREEMENT. SILBERG understands that after executing this
AGREEMENT, he has the right to revoke it within seven (7) days after his
execution of it. SILBERG understands that this AGREEMENT will not become
effective and enforceable unless the seven day revocation period passes and
SILBERG does not revoke the AGREEMENT in writing. SILBERG understands that this
AGREEMENT may not be revoked after the seven (7) day revocation period has
passed. SILBERG understands that any revocation of this AGREEMENT must be made
in writing and received by LIGAND at 10275 Science Center Drive, San Diego, CA
92121, within the seven day period.

     30. EFFECTIVE DATE. This AGREEMENT shall become effective and binding upon
the parties eight (8) days after SILBERG's execution thereof, so long as he has
not revoked it within the time period and in the manner specified in paragraph
29, above.


Dated: JULY 2, 2003                                  /S/ THOMAS H. SILBERG
                                                     ---------------------------
                                                     Thomas H. Silberg



                                                     LIGAND PHARMACEUTICALS INC.

Dated: 7-7-03                                        By:/S/ WARNER R. BROADDUS
                                                     ---------------------------
                                                     VP & General Counsel





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