Exhibit 10.1

RESIGNATION AGREEMENT

This Resignation Agreement (“Agreement”) is hereby entered into by and between
Orexigen Therapeutics, Inc., a Delaware corporation (the “Company”), and Gary D.
Tollefson, M.D., Ph.D. (“Executive”). The Company and Executive are sometimes
referred to herein as a “Party” or collectively as the “Parties.”

RECITALS

WHEREAS, Executive was employed by the Company as its President and Chief
Executive Officer and serves on the Board of Directors of the Company (the
“Board”);

WHEREAS, Executive is currently on a leave of absence, effective November 10,
2008;

WHEREAS, Executive and the Company previously entered into an Employment
Agreement dated as of April 6, 2007, as amended by Amendment No. 1 to Employment
Agreement dated as of August 22, 2007 (together, the “Employment Agreement”);

WHEREAS, Executive and the Company wish to enter into this Agreement for the
purpose of terminating and superseding the Employment Agreement in its entirety;
and

WHEREAS, Executive and the Company wish to terminate their employment
relationship through Executive’s resignation effective as of December 10, 2008
(the “Resignation Date”), and to resolve amicably all of their obligations to
each other, including, without limitation, under the Employment Agreement.

AGREEMENT

NOW, THEREFORE, in consideration of the mutual covenants contained in this
Agreement, and for other good and valuable consideration, the adequacy of which
is hereby acknowledged, the Parties hereby agree as follows:

 

  1. Employment Agreement. The Employment Agreement shall be superseded entirely
by this Agreement, and the Employment Agreement shall be terminated and be of no
further force or effect.

 

  2. Employment and Officer Status. Executive hereby resigns as an employee of
the Company effective as of the Resignation Date. Executive’s separation from
employment shall be reflected in the Company’s records as a voluntary
resignation. Executive hereby resigns from his position as President and Chief
Executive Officer of the Company (and any other officer positions he may hold
with the Company or any of its subsidiaries) effective as of the date hereof.
Executive shall execute any additional documentation necessary to effectuate
such resignation. Executive’s “separation from service” for purposes of
Section 409A of the Internal Revenue Code of 1986, as amended (the “Code”),
shall be the Resignation Date.

 

  3. Resignation from Board. Executive hereby resigns from his position as a
member of the Board effective as of the date hereof. Executive shall execute any
additional documentation necessary to effectuate such resignation.

 

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  4. Compensation.

 

  (a) Base Salary and Accrued Benefits. Prior to or on the Resignation Date, the
Company shall issue to Executive his final paycheck, reflecting (i) his earned
but unpaid base salary through the Resignation Date and (ii) all accrued, unused
vacation due Executive through the Resignation Date. Except as otherwise
provided in this Section 4 and Section 5 below, Executive acknowledges and
agrees that with his final check, Executive will have received all monies,
bonuses, commissions, expense reimbursement, paid time off, or other
compensation he earned or was due during his employment by the Company.

 

  (b) Expense Reimbursements. The Company, within thirty (30) days after the
Resignation Date, will reimburse Executive for any and all reasonable and
necessary business expenses incurred by Executive in connection with the
performance of his job duties prior to the Resignation Date, which expenses
shall be submitted to the Company with supporting receipts and/or documentation
no later than twenty-one (21) days after the Resignation Date.

 

  (c) Benefits. Executive’s entitlement to benefits from the Company, and
eligibility to participate in the Company’s benefit plans, shall cease on the
Resignation Date, except to the extent Executive elects to and is eligible to
receive continued healthcare coverage pursuant to the provisions of the
Consolidated Omnibus Budget Reconciliation Act of 1985, as amended (“COBRA”),
for himself and any covered dependents, at his sole expense in accordance with
the provisions of COBRA.

 

  (d) Equity Awards. As of the Resignation Date, Executive has been granted and
not exercised options to purchase shares of the Company’s common stock pursuant
to the stock option agreements identified on Exhibit A attached hereto (the
“Option Agreements”). In accordance with the terms of such Option Agreements,
and except as set forth in Section 5, on the Resignation Date, Executive’s stock
options shall cease to vest and all of the unvested stock options held by
Executive pursuant to the Option Agreements shall terminate on the earlier of
December 31, 2010, or consummation of a Change of Control (as defined in the
Employment Agreement).

 

  (e) Taxes. Executive understands and agrees that all payments under this
Agreement will be subject to appropriate tax withholding and other deductions,
as and to the extent required by law.

 

  5. Severance Benefits. In exchange for Executive’s agreement to be bound by
the terms of this Agreement, including, but not limited to, the release of
claims in Section 6, Executive shall be entitled to receive the following, which
shall be the exclusive severance benefits to which Executive is entitled, unless
Executive has breached the provisions of this Agreement, in which case the
provisions of Section 18(b) shall apply:

 

  (a) Severance Payments. The Company shall pay to Executive (i) the sum of
$212,500 on the date which is six (6) months following the Resignation Date
(June 10, 2009) and (ii) three (3) installments in the amount of $35,417 each,
payable on July 10, 2009, August 10, 2009, and September 10, 2009.

 

  (b) Payment In Lieu of Bonus. The Company shall pay Executive in a lump sum
the amount of $255,000 in lieu of his 2008 bonus, within five (5) business days
following expiration of the revocation period set forth in Section 6(c)(v) (the
“Effective Date”), provided Executive does not give notice of revocation.

 

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  (c) Relocation Expenses. The Company shall reimburse Executive for reasonable
and customary realtor expenses, closing costs and moving expenses actually
incurred by Executive in connection with the sale of his Del Mar, California
residence on or before the twenty-four (24) month anniversary of the Resignation
Date (provided that the residence has been listed for sale during such time,
without substantial interruptions), in an amount not to exceed $325,000.00. Such
reimbursement shall be conditioned upon receipt by the Company of supporting
receipts and/or documentation and/or receipts in form and substance reasonably
satisfactory to the Company (“Supporting Documentation”). To the extent that any
payments or reimbursements provided to the Executive under this Agreement are
deemed to constitute compensation to which Treasury Regulation
Section 1.409A-3(i)(1)(iv) would apply, such amounts shall be paid or reimbursed
to the Executive within ten (10) business days after the Company’s receipt of
the Supporting Documentation, but in no event later than December 31 of the year
following the year in which the expense is incurred (or such earlier date as is
set forth in this Section 5(c) with respect to such expense). The amount of any
such payments eligible for reimbursement in one year shall not affect the
payments or expenses that are eligible for payment or reimbursement in any other
taxable year, and the Executive’s right to such payments or reimbursement shall
not be subject to liquidation or exchange for any other benefit.

 

  (d) Stock Options. Effective as of the Effective Date (whether before or after
the Resignation Date), the vesting and/or exercisability of each of Executive’s
outstanding options granted pursuant to the Option Agreements shall be
automatically accelerated as to the number of options that would vest over the
twelve (12) month period following the Resignation Date had Executive remained
continuously employed by the Company during such period, as set forth on Exhibit
A. In addition, in the event of a Change in Control on or before December 31,
2010, all of Executive’s outstanding options that were unvested as of the
Resignation Date (after giving effect to the accelerated vesting pursuant to the
preceding sentence) shall vest and become exercisable. In the event that no
Change in Control occurs on or before December 31, 2010, all of the unvested
stock options held by Executive pursuant to the Option Agreements shall
terminate on such date. Following the Resignation Date, Executive’s vested
options shall remain exercisable through December 31, 2010. The foregoing
supersedes any contrary provision in the Option Agreements or any plan under
which such options were issued.

 

  (e) Attorneys’ Fees. The Company shall reimburse Executive’s reasonable and
customary attorney’s fees incurred in connection with the preparation of this
Agreement, in an amount not to exceed $15,000.00. Any amounts payable under this
Section 5(e) shall be made in accordance with Treasury Regulation
Section 1.409A-3(i)(1)(iv) and shall be paid to Executive within ten
(10) business days after the Company’s receipt of notice from Executive as to
the amount of such attorneys’ fees, but in no event later than the last day of
Executive’s taxable year following the taxable year in which Executive incurred
the expenses. The amounts provided under this Section 5(e) during any taxable
year of Executive’s will not affect such amounts provided in any other taxable
year of Executive’s, and Executive’s right to reimbursement for such amounts
shall not be subject to liquidation or exchange for any other benefit.

 

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In the event of Executive’s death prior to payment of any cash amounts due under
Section 4 and Section 5(a), (b) and (e), all such remaining amounts shall be
paid to Executive’s estate within five (5) days of Executive’s death (but in no
event earlier than January 1, 2009). In such event, amounts due under
Section 5(c) shall remain payable for the period set forth therein. In such
event, notwithstanding any contrary provision in the Option Agreements, or any
plan governing such Stock Options, the options covered by the Option Agreement
shall remain exercisable and vest in accordance with Section 5(d).

 

  6. Release by Executive.

 

  (a) General Release of Claims by Executive. As a material inducement for the
Company to enter into this Agreement, and in exchange for the payments provided
for herein, Executive knowingly and voluntarily waives and releases all rights
and claims, known and unknown, which Executive may have against the Company
and/or any of the Company’s related or affiliated entities or successors, or any
of their current or former officers, directors, managers, employees, agents,
insurance carriers, auditors, accountants, attorneys or representatives
(collectively, the “Company Releasees”), including any and all charges,
complaints, claims, liabilities, obligations, promises, agreements, contracts,
controversies, damages, actions, causes of action, suits, rights, demands,
costs, losses, debts and expenses of any kind. This includes, but is not limited
to, claims for employment discrimination, harassment, wrongful termination,
constructive termination, violation of public policy, breach of any express or
implied contract, breach of any implied covenant, fraud, intentional or
negligent misrepresentation, emotional distress, defamation, or any other claims
relating to Executive’s relationship with the Company. This also includes a
release of any claims under any federal, state or local laws or regulations,
including, but not limited to: (1) Title VII of the Civil Rights Act of 1964, 42
U.S.C. § 2000(e) et seq. (race, color, religion, sex, and national origin
discrimination); (2) the Age Discrimination in Employment Act, 29 U.S.C. § 621
et seq. (age discrimination) (“ADEA”); (3) Section 1981 of the Civil Rights Act
of 1866, 42 U.S.C. 1981 (race discrimination); (4) the Equal Pay Act of 1963, 29
U.S.C. § 206 (equal pay); (5) the California Fair Employment and Housing Act,
Cal. Gov’t. Code § 12900, et seq. (discrimination, including race, color,
national origin, ancestry, disability, medical condition, marital status, sex,
sexual orientation; sexual or racial harassment and age); (6) the California
Labor Code § 200, et seq. (salary, commission, compensation, benefits and other
matters); (7) the Fair Labor Standards Act, 29 U.S.C. § 201, et seq. (wage and
hour matters, including overtime pay); (8) COBRA; (9) Executive Order 11141 (age
discrimination); (10) Section 503 of the Rehabilitation Act of 1973, 29 U.S.C. §
701, et seq. (disability discrimination); (11) the Employee Retirement Income
Security Act of 1974, as amended, 29 U.S.C. § 1001, et seq. (employee benefits);
(12) Title I of the Americans with Disabilities Act (disability discrimination);
(13) California Labor Code Section 132(a) (discrimination based on filing a
workers’ compensation claim); (14) California Civil Code § 1786, et seq.
(investigation reports); (15) the Family and Medical Leave Act of 1993, 29
U.S.C. § 2601 et seq.; (16) the False Claims Act , 31 U.S.C. § 3729 et seq.;
(17) the Worker Adjustment and Retraining Notification Act, as amended, 29
U.S.C. § 2101 et seq.; (18) the Sarbanes-Oxley Act of 2002; (19) the California
Equal Pay Law, as amended, Cal. Lab. Code §§ 1197.5(a), 1199.5; (20) the
Moore-Brown-Roberti Family Rights Act of 1991, as amended, Cal. Gov’t Code
§§12945.2, 19702.3; (21) California Labor Code §§ 1101, 1102, 69 Ops. Cal. Atty.
Gen. 80 (1986); (22) California Labor Code §§ 1102.5(a),(b); (23) the California
WARN Act, Cal. Lab. Code § 1400 et seq.; (24) the California False Claims Act,
Cal. Gov’t Code § 12650 et seq.; (25) the California Corporate Criminal
Liability Act, Cal. Penal Code § 387; (26) any applicable California Industrial
Welfare Commission Order (wage matters); (27) federal and state securities laws;
and (28) or any other federal, state or local law of similar effect. The matters
that are the subject of the releases referred to in this Section 6(a) shall be
referred to collectively as the “Released Matters.” This General Release shall
not, however, constitute a waiver of any of Executive’s rights under this
Agreement or claims Executive may have to vested or earned compensation and
benefits under the Company’s employee benefit plans.

 

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  (b) Release of Unknown Claims by Executive. Executive expressly waives all
rights under Section 1542 of the Civil Code of the State of California, which
reads as follows:

A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS WHICH A CREDITOR DOES NOT KNOW OR
SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE, WHICH
IF KNOWN BY HIM OR HER MUST HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH
THE DEBTOR.

With full awareness and understanding of the above provisions, Executive hereby
waives any rights he may have under Section 1542, as well as under any other
statutes or common law principles of similar effect. Executive intends to, and
hereby does, release the Company Releasees from claims which Executive does not
presently know or suspect to exist at this time.

 

  (c) ADEA Matters. Executive understands and acknowledges that:

 

  (i) This Agreement constitutes a voluntary waiver of any and all rights and
claims he has against the Company as of the date of the execution of this
Agreement, including rights or claims arising under the ADEA.

 

  (ii) He has waived rights or claims pursuant to this Agreement and in exchange
for consideration, the value of which exceeds payment or remuneration to which
Executive was already entitled.

 

  (iii) He is hereby advised that he may consult with an attorney of his
choosing concerning this Agreement prior to executing it.

 

  (iv) He has been afforded a period of at least twenty-one (21) days to
consider the terms of this Agreement, and in the event he should decide to
execute this Agreement in fewer than twenty-one (21) days, he has done so with
the express understanding that he has been given and declined the opportunity to
consider this Agreement for a full twenty- one (21) days, and waives the balance
of the twenty-one (21) day period.

 

  (v) He may revoke this Agreement at any time during the seven (7) days
following the date of execution of this Agreement, and this Agreement shall not
become effective or enforceable until such revocation period has expired.
Executive understands that if he revokes this Agreement, he shall not be
entitled to any of the benefits provided by this Agreement.

 

  (d)

No Assignment. Executive warrants and represents that no portion of any of the
Released Matters, and no portion of any recovery or settlement to which
Executive might be entitled, has been assigned or transferred to any other
person, firm or corporation not a party to this Agreement, in any manner,
including by way of subrogation or

 

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operation of law or otherwise. If any claim, action, demand or suit should be
made or instituted against the Company or any affiliate of the Company because
of any such purported assignment, subrogation or transfer, Executive agrees to
indemnify and hold harmless the Company or any affiliate of the Company against
such claim, action, suit or demand, including necessary expenses of
investigation, attorneys’ fees and costs.

 

  7. Limited Release by the Company.

 

  (a) The Company, on behalf of itself and its officers, directors,
shareholders, subsidiaries, and affiliates, hereby knowingly and voluntarily
releases and forever discharges Executive and his heirs, executors, successors,
and assigns from any and all rights, claims, demands, liabilities, actions,
causes of action, and damages of whatever nature whatsoever, known or unknown,
fixed or contingent, in law or in equity, which the Company may have or claim to
have arising out of, based upon, or relating to Executive’s employment by the
Company, or service on the Board of Directors of the Company, other than claims
arising out of, based upon, or relating to Executive’s illegal conduct, fraud,
embezzlement, intentional material misconduct, breach of fiduciary duty, or
actions taken without due authorization.

 

  (b) Release of Unknown Claims by the Company. Subject to the limitations of
Section 7(a), the Company expressly waives all rights under Section 1542 of the
Civil Code of the State of California, which reads as follows:

A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS WHICH A CREDITOR DOES NOT KNOW OR
SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE, WHICH
IF KNOWN BY HIM OR HER MUST HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH
THE DEBTOR.

With full awareness and understanding of the above provisions, the Company
hereby waives any rights it may have under Section 1542, as well as under any
other statutes or common law principles of similar effect, subject to the
limitations of Section 7(a). The Company intends to, and hereby does, release
Executive from claims which it does not presently know or suspect to exist at
this time, subject to the limitations of Section 7(a).

 

  8.

Proprietary Information. Executive acknowledges that certain information,
observations and data obtained by him during the course of or related to his
employment with the Company (including, without limitation, information with
respect to the Company’s and its affiliates’ operations, processes, products,
inventions, business practices, finances, vendors, suppliers, customers,
potential customers, stockholders, business plans, marketing plans, proposals or
methods, costs, prices, contractual relationships, regulatory status,
compensation paid to employees or other terms of employment) are the sole
property of the Company and constitute trade secrets of the Company. Promptly
following the execution of this Agreement (but in any event within five
(5) days), Executive agrees to return all files, customer lists, financial
information or other Company documentation (excluding documents that have been
publicly filed with the Securities and Exchange Commission) which are in
Executive’s possession or control without making copies thereof. Except as
required pursuant to applicable law, rule or regulation or other legal
compulsion or in order to assert any rights under this Agreement, Executive
further agrees that he will not disclose to any person or use for his own
account any of the above described trade secret

 

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information, observations or data without the written consent of the Board.
Further, Executive acknowledges that any unauthorized use of the above described
confidential information will cause irreparable harm to the Company and its
affiliates and will give rise to an immediate action by any of them for
injunctive relief. Executive acknowledges that he continues to be bound by the
Proprietary Information and Inventions Agreement that he signed in connection
with his employment, in accordance with the terms thereof.

 

  9. Noninterference. For a period of one (1) year following the Resignation
Date, Executive agrees not to interfere with the business of the Company by
(a) soliciting or attempting to solicit any employee or consultant of the
Company to terminate such employee’s or consultant’s employment or service in
order to become an employee, consultant or independent contractor to or for any
competitor of the Company or (b) soliciting or attempting to solicit any client,
customer or other person either directly or indirectly, to direct his or its
purchase of the Company’s products and/or services to any person, firm,
corporation, institution or other entity in competition with the business of the
Company.

 

  10. Cooperation Clause. Executive agrees to provide reasonable assistance to
the Company (including the Board and any committees thereof) and its counsel and
accountants in any financial audits or internal investigation involving
securities, financial, accounting, or other matters, and in its defense of, or
other participation in, any administrative, judicial, or other proceeding
arising from any charge, complaint or other action which has been or may be
filed relating to the period during which Executive was employed by the Company.
The Company agrees to reimburse Executive for his reasonable and actual expenses
incurred in providing any cooperation or assistance contemplated by this
Agreement, and if such services exceed eight (8) hours in any calendar month to
pay to Executive $250 per hour for each additional hour of service; provided,
however, that the Company shall have no obligation to compensate Executive under
this Section 10 for his cooperation or assistance in any matter in which he is
named as a defendant or respondent, or with respect to which Executive requests
indemnification pursuant to Section 15.

 

  11. Confidentiality of Agreement. Except as expressly set forth in Section 12
or to the extent required to comply with applicable legal requirements
(including the terms of the listing of the Company’s stock), neither Party shall
issue any press release or make any public statement regarding the matters
contemplated hereby without the prior approval of the other Party. The Parties
acknowledge that this Agreement must be filed by the Company with the Securities
and Exchange Commission as an exhibit to its next periodic or current report,
and Executive hereby consents to such filing.

 

  12. Press Release; Mutual Nondisparagement. If the Company issues any press
release regarding Executive’s departure from its Company following the date
hereof, the Company shall allow Executive to review and approve it in advance.
Executive agrees to present a positive public image regarding the Company and
not to disparage or otherwise publish or communicate negative statements or
opinions about the Company in any way. Company agrees to present a positive
public image regarding Executive and not to disparage or otherwise publish or
communicate negative statements or opinions about Executive in any way. For
purposes of this Section 12, internal communications between or among management
personnel, officers, and directors of the Company are not subject to the
preceding sentence. Except as required by law or authorized in advance by the
Board, Executive shall not communicate, directly or indirectly, with
stockholders of the Company or their representatives concerning the management
of the Company, the operations of the Company, the development programs of the
Company or the financial status of the Company.

 

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  13. Application of Insider Trading Policies Applicable to Executive. On the
third business day following the earlier of (i) the Company’s release of the
one-year data from its NB-302 clinical trial, or (ii) the Company’s financial
results press release with respect to the year and quarter ending December 31,
2008, Executive will be released from the Company’s insider trading policy.
Executive acknowledges that he is aware of the prohibitions on insider trading
contained in the federal securities laws.

 

  14. Section 16. Executive acknowledges that following the date hereof he will
continue to be subject to certain provisions of Section 16 of the Securities
Exchange Act of 1934, as amended, and he agrees to comply with such provisions.
Absent a legal determination to the contrary, the Company’s records will show
that the date hereof was the last date that Executive was an “executive officer”
of the Company (as such term is defined under the Securities Exchange Act of
1934, as amended).

 

  15. Indemnification. Executive will continue to be indemnified by any
applicable insurance policies, agreements, certificate of incorporation, or
bylaws of the Company and as otherwise required by law for his actions as an
employee, officer, and director prior to the Resignation Date to the same extent
as during his employment to the fullest extent provided by law.

 

  16. Return of Equipment. Within five (5) days of the Resignation Date,
Executive shall return to the Company in good working order any equipment,
instruments, or accessories of the Company in his custody for the purpose of
conducting the business of the Company without deleting, removing, or
duplicating any data reflecting the Company’s proprietary information, or if not
returned, account to the Company to its reasonable satisfaction for all such
equipment, instruments, or accessories.

 

  17. Dispute Resolution. Unless otherwise prohibited by law or specified below,
all disputes, claims and causes of action, in law or equity, arising from or
relating to this Agreement or the Employment Agreement or their enforcement,
performance, breach, or interpretation shall be resolved solely and exclusively
by final and binding arbitration held in San Diego, California through JAMS
(“JAMS”) under the then existing JAMS Employment Arbitration Rules and
Procedures. However, nothing in this Section is intended to prevent either party
from obtaining injunctive relief in court to prevent irreparable harm pending
the conclusion of any such arbitration. Each party in any such arbitration shall
be responsible for its own attorneys’ fees, costs and necessary disbursement;
provided, however, that if one party refuses to arbitrate and the other party
seeks to compel arbitration by court order, if such other party prevails, it
shall be entitled to recover reasonable attorneys’ fees, costs and necessary
disbursements. Pursuant to California Civil Code Section 1717, each party
warrants that it was represented by counsel in the negotiation and execution of
this Agreement, including the attorneys’ fees provision herein.

 

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  18. Miscellaneous Provisions.

 

  (a) The provisions of this Agreement are severable. If any provision is held
to be invalid or unenforceable it shall not affect the validity or
enforceability of any other provision.

 

  (b) If Executive materially violates any provision of this Agreement (and such
violation, if unintentional on the part of Executive, continues for a period of
thirty (30) days following receipt of written notice from the Company), any
severance payments then or thereafter due from the Company to Executive may be
terminated forthwith and upon such election by the Company, the Company’s
obligation to pay and Executive’s right to receive such severance payments shall
terminate and be of no further force or effect. Executive’s obligations under
this Agreement shall not be limited or affected by, and such provisions shall
remain in full force and effect notwithstanding the termination of any severance
payments by the Company in accordance with this Section 18(b). The exercise of
the right to terminate such payments shall not be deemed to be an election of
remedies by the Company and shall not in any manner modify, limit or preclude
the Company from exercising any other rights or seeking any other remedies
available to it at law or in equity. Notwithstanding the foregoing, in the event
the Company elects to exercise its termination rights hereunder, it shall
promptly (i) remit any withheld payments into a separate account and notify
Executive thereof in writing and (ii) unless otherwise agreed with Executive,
commence a declaratory relief action seeking an appropriate court determination
of the validity of such interpretation.

 

  (c) Except as expressly stated herein, this Agreement, the Proprietary
Information and Inventions Agreement between the Company and Executive and the
exhibits hereto and thereto represent the sole and entire agreement between the
Parties with respect to the subject matters contained herein and therein and
supersede all prior documents, agreements, negotiations and discussions between
the Parties with respect to the subject matters contained herein and therein.
The Parties acknowledge and agree that there are no collateral agreements or
representations, written or oral, regarding the terms and conditions of
Executive’s employment with the Company, the separation of Executive’s
employment with the Company, and settlement of all claims between the Parties
other than those expressly set forth in this Agreement and the Proprietary
Information and Inventions Agreement between the Company and Executive. This
Agreement supersedes and terminates the Employment Agreement. Upon the Parties’
execution of this Agreement, neither Party shall have any further obligation to
the other under the Employment Agreement.

 

  (d) No provision of this Agreement may be altered, modified or amended unless
such alteration, modification, or amendment is agreed to in writing and signed
by Executive on the one hand and an executive officer of the Company on the
other, which writing expressly states the intent of the Parties to modify this
Agreement.

 

  (e) This Agreement shall be construed as a whole in accordance with its fair
meaning and in accordance with the laws of the State of California. Any suit
brought hereon shall be brought in the state or federal courts sitting in San
Diego County, California, the Parties hereby waiving any claim or defense that
such forum is not convenient or proper. Each party hereby agrees that any such
court shall have in personam jurisdiction over it and consents to service of
process in any manner authorized by California law.

 

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  (f) The language in this Agreement shall not be construed for or against any
particular Party. The headings used herein are for reference only and shall not
affect the construction of this Agreement. This Agreement has been drafted by
legal counsel representing the Company, but Executive has participated in the
negotiation of its terms, and, therefore, the normal rule of construction to the
effect that any ambiguities are to be resolved against the drafting party shall
not be employed in the interpretation of this Agreement.

 

  (g) No waiver by any Party hereto at any time of any breach of, or compliance
with, any condition or provision of this Agreement to be performed by any other
Party hereto shall be deemed a waiver of similar or dissimilar provisions or
conditions at the same or at any prior or subsequent time.

 

  (h) This Agreement may be executed in one or more counterparts, and by
facsimile, each of which shall be deemed to be an original as against any Party
that has signed it, but all of which together will constitute one and the same
instrument.

 

  (i) Executive acknowledges that the payments and benefits provided in this
Agreement may have tax ramifications to him. The Company has provided no tax or
other advice to Executive on such matters and Executive is free to consult with
an accountant, legal counsel, or other tax advisor regarding the tax
consequences he may face.

 

  (j) EXECUTIVE ACKNOWLEDGES THAT HE HAS READ THIS AGREEMENT CAREFULLY,
UNDERSTANDS ALL OF ITS TERMS, AND AGREES TO THOSE TERMS KNOWINGLY, FREELY,
VOLUNTARILY, AND WITHOUT DURESS.

 

  (k) Any and all notices or other communications or deliveries required or
permitted to be given or made shall be in writing and delivered personally, or
sent by certified or registered mail, return receipt requested and postage
prepaid, or sent by overnight courier service as follows:

If to the Company, at:

Orexigen Therapeutics, Inc.

3344 N. Torrey Pines Court, Suite 200

La Jolla, California 92037

Attention: General Counsel

If to Executive, at:

Gary D. Tollefson, M.D., Ph.D.

9052 Diamond Pointe Drive

Indianapolis, IN 46236

or at such other address as any party may specify by notice given to such other
party in accordance with this Section 18(k). The date of giving of any such
notice shall be the date of hand delivery, five days after the date of the
posting of the mail or the day immediately following the date when deposited
with the overnight courier.

 

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  (l) To the extent the payments and benefits under this Agreement are subject
to Section 409A of the Code, this Agreement shall be interpreted, construed and
administered in a manner that satisfies the requirements of Sections 409A(a)(2),
(3) and (4) of the Code and the Treasury Regulations thereunder (and any
applicable transition relief under Section 409A of the Code). As provided in
Internal Revenue Notice 2007-86, notwithstanding any other provision of this
Agreement, with respect to an election or amendment to change a time or form of
payment under this Agreement made on or after January 1, 2008 and on or before
December 31, 2008, the election or amendment shall apply only with respect to
payments that would not otherwise be payable in 2008, and shall not cause
payments to be made in 2008 that would not otherwise be payable in 2008.

 

  (m) Executive expressly agrees and acknowledges that if any taxes are imposed
upon Executive under Section 409A of the Code in respect of any compensation or
benefits payable to the Executive, whether in connection with this Agreement or
otherwise, then (i) the payment of such taxes shall be solely the Executive’s
responsibility, and (ii) neither the Company, its affiliated entities nor any of
their respective past or present directors, officers, employees or agents shall
have any liability for any such taxes.

 

[Signature Page Follows]

 

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IN WITNESS WHEREOF, the Parties hereto have executed this Agreement on the dates
indicated below.

 

EXECUTIVE     OREXIGEN THERAPEUTICS, INC. /s/ Gary D. Tollefson     By:   /s/
Eckard Weber Gary D. Tollefson, M.D., Ph.D.     Name:   Eckard Weber, M.D.,    
  Its:   Executive Chairman and Interim     President and Chief Executive
Officer     Dated: December 4, 2008     Dated: December 4, 2008 APPROVED AS TO
FORM:         STRADLING YOCCA CARLSON & RAUTH     LATHAM & WATKINS LLP By:   /s/
Lawrence B. Cohn     By:   /s/ Mark S. Pulliam   Lawrence B. Cohn       Mark S.
Pulliam Attorney for Gary D. Tollefson, M.D., Ph.D.     Attorney for Orexigen
Therapeutics, Inc.         Dated: December 4, 2008     Dated: December 4, 2008

 

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EXHIBIT A

STOCK OPTION AGREEMENTS

 

1. Notice of Stock Option Grant and Stock Option Agreement (No.8—NQ) dated
May 27, 2005 granting option to purchase 408,434 shares (subsequently converted
into 204,217 shares following one-for-two reverse stock split) of the Company’s
common stock. Effective as of the Effective Date, the option shall be vested and
exercisable (after accounting for the acceleration of the vesting and
exercisability of such option pursuant to Section 5(d) of the Agreement) as to
174,217 of the shares subject thereto. (Options for 30,000 shares previously
exercised.)

 

2. Notice of Stock Option Grant and Stock Option Agreement (No. 9—ISO) dated
May 27, 2005 granting option to purchase 1,333,332 shares (subsequently
converted into 666,666 shares following one-for-two reverse stock split) of the
Company’s common stock. Effective as of the Effective Date, the option shall be
vested (after accounting for the acceleration of the vesting and exercisability
of such option pursuant to Section 5(d) of the Agreement) as to 666,666 of the
shares subject thereto.

 

3. Notice of Stock Option Grant and Stock Option Agreement (No. 180—NQ) dated
September 28, 2006 granting option to purchase 400,000 shares (subsequently
converted into 200,000 shares following one-for-two reverse stock split) of the
Company’s common stock. Effective as of the Effective Date, the option shall be
vested (after accounting for the acceleration of the vesting and exercisability
of such option pursuant to Section 5(d) of the Agreement) as to 162,500 of the
shares subject thereto.

 

4. Notice of Stock Option Grant and Stock Option Agreement (No. 181—ISO) dated
December 20, 2007 granting option to purchase 18,699 shares of the Company’s
common stock. Effective as of the Effective Date, the option shall be vested
(after accounting for the acceleration of the vesting and exercisability of such
option pursuant to Section 5(d) of the Agreement) as to 4,675 of the shares
subject thereto.

 

5. Notice of Stock Option Grant and Stock Option Agreement (No. 182—NQ) dated
December 20, 2007 granting option to purchase 61,301 shares of the Company’s
common stock. Effective as of the Effective Date, the option shall be vested
(after accounting for the acceleration of the vesting and exercisability of such
option pursuant to Section 5(d) of the Agreement) as to 35,325 of the shares
subject thereto.

 

6. Notice of Stock Option Grant and Stock Option Agreement (No. 183 – NQ) dated
August 15, 2008 granting option to purchase 310,000 shares of the Company’s
common stock. Effective as of the Effective Date, the option shall be vested
(after accounting for the acceleration of the vesting and exercisability of such
option pursuant to Section 5(d) of the Agreement) as to 96,875 of the shares
subject thereto.

 

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