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UNITED STATES SECURITIES AND
    EXCHANGE COMMISSION
 Washington, D.C.
    20549
      Form 10-K
      (Mark One)þ

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
    SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended
    December 31, 2007Oro

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
    SECURITIES EXCHANGE ACT OF 1934For the transition period
    from          to   Commission file number
    001-33415
  OREXIGEN THERAPEUTICS,
    INC.
 (Exact name of registrant as
    specified in its charter)
  Delaware(State or Other Jurisdiction
    of
    Incorporation or Organization)

65-1178822(I.R.S. Employer
    Identification No.)12481 High Bluff Drive, Suite 160,
    San Diego, California(Address of Principal
    Executive Offices)

92130(Zip
    Code)  (858) 436-8600
 (Registrants Telephone Number, Including Area Code)
  Securities registered pursuant to Section 12(b) of the
    Act:
  Title of Each Class

Name of Exchange on Which RegisteredCommon Stock, $.001 par value

The NASDAQ Stock Market LLC   Securities registered pursuant to Section 12(g) of the
    Act:
  None
  o þ
  o þ
  þ o
  Regulation S-K Form 10-K Form 10-K. o
  Rule 12b-2
  Large accelerated
    filer o

Accelerated
    filer o

Non-accelerated filer
    þ
    
    (Do not check if a smaller reporting company)

Smaller reporting company
    o   Rule 12b-2 o þ
      DOCUMENTS INCORPORATED BY REFERENCE




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##### 





OREXIGEN
    THERAPEUTICS, INC.
  FORM 10-K
    FOR THE FISCAL YEAR ENDED DECEMBER 31, 2007
  TABLE OF
    CONTENTS
   
 PagePART IItem 1.


Business


1Item 1A.


Risk Factors


37Item 1B.


Unresolved Staff Comments


66Item 2.


Properties


66Item 3.


Legal Proceedings


66Item 4.


Submission of Matters to a Vote of Security
    Holders


67PART IIItem 5.


Market for Registrants Common Equity,
    Related Stockholder Matters and Issuer Purchases of Equity
    Securities


67Item 6.


Selected Financial Data


70Item 7.


Managements Discussion and Analysis of
    Financial Condition and Results of Operations


71Item 7A.


Quantitative and Qualitative Disclosures About
    Market Risk


80Item 8.


Financial Statements and Supplementary Data


81Item 9.


Changes in and Disagreements with Accountants on
    Accounting and Financial Disclosure


109Item 9A.


Controls and Procedures


109Item 9B.


Other Information


109PART IIIItem 10.


Directors, Executive Officers and Corporate
    Governance


109Item 11.


Executive Compensation


110Item 12.


Security Ownership of Certain Beneficial Owners
    and Management and Related Stockholder Matters


110Item 13.


Certain Relationships and Related Transactions ,
    and Director Independence


110Item 14.


Principal Accounting Fees and Services


110PART IVItem 15.


Exhibits, Financial Statement Schedules


110Signatures





113EXHIBIT 10.2EXHIBIT 23.1EXHIBIT 31.1EXHIBIT 31.2EXHIBIT 32.1




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PART 1



FORWARD-LOOKING
    STATEMENTS  Form 10-K . Form 10-K
  Form 10-K
  Item 1.
    Business.  Overview
  tm tm tm
   1




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and/or
  end-of-Phase-II
    The
    Obesity Epidemic
   2




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Limitations
    of Current Obesity Therapies
     3




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over-the-counter
    The
    Orexigen Solution for Obesity
       4




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##### Table of Contents



in vitro in vitro
  Our
    Product Candidates
    Stage ofProduct Candidate

Drug Components

Indication

Trials Completed

Development

Commercial RightsContrave

Bupropion SR/ Naltrexone SR

Obesity

Phase II,
    Phase IIb

Phase III

Orexigen (worldwide)Empatic

Bupropion SR/ Zonisamide SR

Obesity

Phase II,
    Phase IIb

Phase IIb

Orexigen (worldwide)OREX-003

Olanzapine/ Zonisamide SR

Mitigation of weight gain associated with antipsychotic therapy

Preclinical

Phase II
    Planned for
    2008

Orexigen (worldwide)OREX-004

Naltrexone SR/ Fluoxetine

Obsessive-compulsive disorder

Preclinical

Phase II
    Planned for
    2008

Orexigen (worldwide)   Contrave
     5




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Scientific
    Rationale
       6




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##### Table of Contents



Contrave
    Clinical Results
  Phase II Clinical Trial.
  
    combination therapy, which consisted of 50mg naltrexone IR plus
    300mg bupropion SR;
    bupropion monotherapy, which consisted of 300mg bupropion SR
    plus placebo;
    naltrexone monotherapy, which consisted of 50mg naltrexone IR
    plus placebo; and
    placebo, which consisted of two placebo pills.    intent-to-treat intent-to-treat
 7




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##### Table of Contents



intent-to-treat
  Contrave
    Phase II Mean Weight Loss through 24 WeeksIntent-to-Treat
    Population
  
  Contrave
    Phase II Mean Weight Loss through 24 Weeks
    Completer Population
  
   8




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Phase IIb Clinical Trial.
      
    48mg naltrexone IR plus 400mg bupropion SR;
    16mg naltrexone IR plus 400mg bupropion SR;
    bupropion monotherapy, which consisted of 400mg bupropion SR
    plus placebo;
    naltrexone monotherapy, which consisted of 48mg naltrexone IR
    plus placebo; and
    placebo, which consisted of two placebo pills.    intent-to-treat
   9




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##### Table of Contents



intent-to-treat
  Contrave
    Phase IIb Mean Weight Loss at 24 WeeksIntent-to-Treat
    Population
  
    *
    
    Calculated on the basis of unadjusted least-squares mean
    methodology.  cause-and-effect
  Contrave
    Phase IIb Mean Weight Loss at 24 Weeks
    Completer Population
  
    *
    
    Calculated on the basis of unadjusted least-squares mean
    methodology. 10




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(intent-to-treat intent-to-treat
  intent-to-treat intent-to-treat
  intent-to-treat
  intent-to-treat intent-to-treat
 11




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intent-to-treat
  Contrave
    Phase IIb Mean Weight Loss at 48 WeeksIntent-to-Treat
    Population
  
    *
    
    Calculated on the basis of unadjusted least-squares mean
    methodology.  Contrave
    Phase IIb Mean Weight Loss at 48 Weeks
    Completer Population
  
    *
    
    Calculated on the basis of unadjusted least-squares mean
    methodology. 12




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(intent-to-treat intent-to-treat intent-to-treat
  Contrave
    Phase IIb Mean Weight Loss Over 48 WeeksIntent-to-Treat
    Population
  
  Contrave
    Phase IIb Mean Weight Loss Over 48 Weeks
    Completer Population
  
     13




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sub-study,
      Contrave
    Phase III Clinical Development Program
  end-of-Phase-II
  efficacy-to-side-effects
    
    NB-301:  This trial is designed to study the
    effect of Contrave in generally healthy obese patients utilizing
    the two lower doses of Contrave. We commenced enrollment for
    this trial in the fourth quarter of 2007 and expect to enroll
    approximately 1,650 patients at 34 sites. Patients are
    being blindly randomized to one of two doses of Contrave (16mg
    naltrexone SR or 32mg naltrexone SR plus 360mg bupropion SR) or
    placebo. We intend to analyze as co-primary endpoints for this
    trial the percent change in body weight and percent of patients
    who achieve 5% weight loss, in each case 56 weeks after the
    start of treatment. 14




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##### Table of Contents




    NB-302:  This trial is designed to study the
    effect of Contrave in generally healthy obese patients in
    combination with an intensive behavior modification protocol,
    including dietary counseling, behavioral therapy and exercise.
    We completed enrollment of this trial in November 2007 with
    793 patients at nine sites. Patients have been blindly
    randomized to one of two treatment arms: Contrave (32mg
    naltrexone SR plus 360mg bupropion SR) plus behavior
    modification or placebo plus behavior modification. We intend to
    analyze as co-primary endpoints for this trial the percent
    change in body weight and percent of patients who achieve 5%
    weight loss, in each case 56 weeks after the start of
    treatment.
    NB-303:  This trial is designed to study the
    effect of Contrave in generally healthy obese patients, with a
    provision for dose escalation for non-responders. We commenced
    enrollment for this trial in the fourth quarter of 2007 and
    expect to enroll approximately 1,500 patients at 36 sites.
    Patients are being blindly randomized initially to either
    Contrave (32mg naltrexone SR plus 360mg bupropion SR) or
    placebo. After 28 weeks of treatment, Contrave patients who
    have not achieved at least 5% weight loss will be blindly
    re-randomized to receive either a higher dose of Contrave (48mg
    naltrexone SR plus 360mg bupropion SR) or remain on the original
    dose. We intend to analyze as co-primary endpoints for this
    trial the percent change in body weight and percent of patients
    who achieve 5% weight loss, in each case 56 weeks after the
    start of treatment.
    NB-304:  This trial is designed to study the
    effect of Contrave in obese patients with Type II diabetes.
    We commenced enrollment for this trial in the second quarter of
    2007 and expect to enroll approximately 525 patients at 53
    sites. Patients are being blindly randomized to either Contrave
    (32mg naltrexone SR plus 360mg bupropion SR) or placebo. We
    intend to analyze as co-primary endpoints for this trial the
    percent change in body weight and percent of patients who
    achieve 5% weight loss, in each case 56 weeks after the
    start of treatment. Recent studies have demonstrated that
    obesity is a leading risk factor for various metabolic
    disorders, such as diabetes, and this trial will evaluate
    several factors related to glucose metabolism as secondary
    endpoints.      Contrave SR Formulation Development. max and/or
  under-the-curve, max
 15




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Planned Mechanistic Study.
  Empatic
      max
  Scientific
    Rationale
   16




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Empatic
    Clinical Results
  Phase II Clinical Trial. proof-of-concept
  
    combination therapy, which consisted of 300mg bupropion SR plus
    400mg zonisamide IR; or
    zonisamide monotherapy, which consisted of 400mg zonisamide IR
    plus placebo.    intent-to-treat intent-to-treat
 17




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intent-to-treat
  Empatic
    Phase II Mean Weight Loss Over 24 WeeksIntent-to-Treat
    Population
  
  Empatic
    Mean Weight Loss Over 24 Weeks
    Phase II Completer Population
  
   18




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Phase IIb Clinical Trial. intent-to-treat
  
    120mg zonisamide SR plus 280mg bupropion SR;
    240mg zonisamide SR plus 280mg bupropion SR;
    360mg zonisamide SR plus 280mg bupropion SR;
    120mg zonisamide SR plus 360mg bupropion SR;
    240mg zonisamide SR plus 360mg bupropion SR;
    360mg zonisamide SR plus 360mg bupropion SR; and
    placebo, which consisted of two placebo pills. 19




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intent-to-treat
  Empatic
    Phase IIb Mean Weight Loss at 24 WeeksIntent-to-Treat
    Population
  
  Empatic
    Phase IIb Mean Weight Loss at 24 Weeks
    Completer Population
  
   20




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intent-to-treat
  intent-to-treat 
  Empatic
    Phase IIb Mean Weight Loss at 48 WeeksIntent-to-Treat 
    Double Blind Extension Population
  
    *
    
    Placebo weight loss at 24 weeks; see discussion of study
    design below. 21




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Empatic
    Phase IIb Mean Weight Loss at 48 Weeks
    Completer  Double Blind Extension
    Population
  
    *
    
    Placebo weight loss at 24 weeks; see discussion of study
    design below.    intent-to-treat
  
   22




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Future
    Empatic Clinical Development Plans
    and/or
  Earlier
    Stage Programs
   23




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OREX-003:
    Olanzapine/Zonisamide SR for the Mitigation of Weight Gain
    Associated with Antipsychotic Therapy
        proof-of-concept
  OREX-004:
    Naltrexone SR/Fluoxetine for Obsessive-Compulsive
    Disorder
    and/or
 24




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proof-of-concept
  Sales and
    Marketing
    mild-to-moderately
   25




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Intellectual
    Property
  and/or
    and/or
  intent-to-use
 26




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intent-to-use
    Licensing
    Agreements
  Oregon
    Health & Science University License
    Agreement
      and/or
 27




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and/or
  in vitro
    Lee
    Dante License Agreement
        and/or
 28




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Duke
    University License Agreement
        and/or
  Cypress
    Bioscience, Inc. License Agreement
     29




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Manufacturing
      proposal-by-proposal
     30




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Competition
        over-the-counter
       31




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Third-Party
    Reimbursement
    Medicaid
      Medicare
  over-the-counter
  Private
    Commercial Plans
   32




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out-of-pocket
    Government
    Regulation
      New
    Drug Approval (NDA)
    
    completion of preclinical laboratory and animal testing in
    compliance with the FDAs good laboratory practice, or GLP,
    regulations;
    submission to the FDA of an investigational new drug, or IND,
    application for human clinical testing which must become
    effective before human clinical trials may begin;
    performance of adequate and well-controlled human clinical
    trials to establish the safety and efficacy of the proposed drug
    product for each intended use;
    satisfactory completion of an FDA pre-approval inspection of the
    facility or facilities at which the product is produced to
    assess compliance with the FDAs current Good Manufacturing
    Practice, or cGMP, regulations; and
    submission to and approval by the FDA of an NDA application.     33




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
    Phase I:  Studies are initially conducted in a
    limited population to test the product candidate for safety,
    dose tolerance, absorption, metabolism, distribution and
    excretion in healthy humans or, on occasion, in patients, such
    as cancer patients.
    Phase II:  Studies are generally conducted in a
    limited patient population to identify possible adverse effects
    and safety risks, to determine the efficacy of the product for
    specific targeted indications and to determine dose tolerance
    and optimal dosage. Multiple Phase II clinical trials may
    be conducted by the sponsor to obtain information prior to
    beginning larger and more expensive Phase III clinical
    trials.
    Phase III:  These are commonly referred to as
    pivotal studies. When Phase II evaluations demonstrate that
    a dose range of the product is effective and has an acceptable
    safety profile, Phase III clinical trials are undertaken in
    large patient populations to further evaluate dosage, to provide
    substantial evidence of clinical efficacy and to further test
    for safety in an expanded and diverse patient population at
    multiple, geographically-dispersed clinical trial sites.
    Phase IV:  In some cases, FDA may condition
    approval of an NDA for a product candidate on the sponsors
    agreement to conduct additional clinical trials after NDA
    approval. Such post approval trials are typically referred to as
    Phase IV studies.  and/or
    Section 505(b)(2)
    New Drug Applications
   34




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Manufacturing
    cGMP Requirements
     35




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Other
    Regulatory Requirements
      direct-to-consumer
      DEA
    Regulation
   36




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Employees
    About
    Orexigen
  (858) 436-8600. Form 10-K.
  Available
    Information
  Form 10-K, Form 10-Q, Form 8-K
  1-800-SEC-0330. http://www.sec.gov.
  Item 1A.
    Risk
    Factors.  You should carefully consider the following risk factors, as
    well as the other information in this report, before deciding
    whether to purchase, hold or sell shares of our common stock.
    The occurrence of any of the following risks could harm our
    business, financial condition, results of operations
    and/or
    growth prospects or cause our actual results to differ
    materially from those contained in forward-looking statements we
    have made in this report and those we may make from time to
    time. You should consider all of the factors described when
    evaluating our business.
  Risks
    Related to Our Business and Industry
  We are
    largely dependent on the success of our two obesity product
    candidates in clinical development:
    Contravetm(naltrexone/bupropion, each in a sustained release, or SR,
    formulation) and
    Empatictm(zonisamide SR/bupropion SR). We cannot be certain that either
    product candidate will receive regulatory approval or be
    successfully commercialized.
   37




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
    the FDA may not deem a product candidate safe and effective;
    the FDA may not find the data from preclinical studies and
    clinical trials sufficient to support approval;
    the FDA may require additional preclinical or clinical studies;
    the FDA may not approve of our third-party manufacturers
    processes and facilities; or
    the FDA may change its approval policies or adopt new
    regulations.    Our
    clinical trials may fail to demonstrate acceptable levels of
    safety and efficacy of our product candidates, which could
    prevent or significantly delay their regulatory
    approval.
    end-of-Phase-II
 38




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Our
    bioequivalence studies may fail to demonstrate acceptable
    comparability between different formulations of Contrave used in
    our Phase III clinical trials and between formulations of
    Contrave used in our Phase III clinical trials and the
    formulation of Contrave we intend to launch
    commercially.
    Our
    product candidates may cause undesirable side effects or have
    other properties that could delay or prevent their regulatory
    approval or limit the commercial profile of any approved
    label.
   39




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
    regulatory authorities may withdraw their approval of the
    product;
    regulatory authorities may require the addition of labeling
    statements, such as a black box warning with
    Contrave or Empatic or a contraindication; 40




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
    we may be required to create a Medication Guide outlining the
    risks of such side effects for distribution to patients;
    we may be required to change the way the product is
    administered, conduct additional clinical trials or change the
    labeling of the product;
    we could be asked to formulate a risk evaluation mitigation
    strategy that could include a program of post-marketing
    surveillance or restricted distribution for patients receiving
    our products;
    we could be sued and held liable for injury caused to
    individuals exposed to or taking our product candidates; and
    our reputation may suffer.    Delays
    in the commencement or completion of clinical testing could
    result in increased costs to us and delay or limit our ability
    to generate revenues.
    
    obtaining regulatory approval to commence a clinical trial;
    reaching agreement on acceptable terms with prospective contract
    research organizations, or CROs, and trial sites, the terms of
    which can be subject to extensive negotiation and may vary
    significantly among different CROs and trial sites;
    manufacturing sufficient quantities of a product candidate for
    use in clinical trials;
    obtaining institutional review board, or IRB, approval to
    conduct a clinical trial at a prospective site;
    recruiting and enrolling patients to participate in clinical
    trials for a variety of reasons, including competition from
    other clinical trial programs for the treatment of obesity or
    similar indications; and
    retaining patients who have initiated a clinical trial but may
    be prone to withdraw due to side effects from the therapy, lack
    of efficacy or personal issues, or who are lost to further
    follow-up.    
    failure to conduct the clinical trial in accordance with
    regulatory requirements or our clinical protocols;
    inspection of the clinical trial operations or trial sites by
    the FDA or other regulatory authorities resulting in the
    imposition of a clinical hold;
    unforeseen safety issues; and
    lack of adequate funding to continue the clinical trial.   41




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Our
    product candidates are combinations of generically-available
    pharmaceutical products, and our success is dependent on our
    ability to compete against off-label generic substitutes and
    demonstrate the advantages of our proprietary combination
    products.
    and/or and/or
    We
    rely primarily on third parties to conduct our clinical trials.
    If these third parties do not successfully carry out their
    contractual duties or meet expected deadlines, we may not be
    able to obtain regulatory approval for or commercialize our
    product candidates within our expected timeframes or at
    all.
   42




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We
    expect intense competition in the obesity marketplace for
    Contrave and Empatic, and new products may emerge that provide
    different or better therapeutic alternatives for obesity and
    weight loss.
  over-the-counter over-the-counter
        
    research and development resources, including personnel and
    technology;
    regulatory experience;
    drug development and clinical trial experience;
    experience and expertise in exploitation of intellectual
    property rights; and
    capital resources.   43




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We
    have limited sales and marketing experience or resources, and we
    may not be able to effectively market and sell our
    products.
    Our
    development and commercialization strategy depends upon access
    to findings of safety and effectiveness based on data not
    developed by us but which the FDA may reference in reviewing our
    U.S. marketing applications. In territories outside the United
    States, we must either negotiate access to these safety and
    effectiveness findings or develop them ourselves.
     44




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Even
    if our product candidates receive regulatory approval, they may
    still face future development and regulatory
    difficulties.
    
    issue warning letters or untitled letters;
    impose civil or criminal penalties;
    suspend regulatory approval;
    suspend any ongoing clinical trials;
    refuse to approve pending applications or supplements to
    applications filed by us;
    impose restrictions on operations, including costly new
    manufacturing requirements; or
    seize or detain products or require us to initiate a product
    recall. 45




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Even
    if our product candidates receive regulatory approval in the
    United States, we may never receive approval or commercialize
    our products outside of the United States.
  follow-up
  If the
    suppliers upon whom we rely for active pharmaceutical
    ingredients, or API, fail to produce such ingredients in the
    volumes that we require on a timely basis, or to comply with
    stringent regulations applicable to pharmaceutical drug
    manufacturers, we may face delays in the conduct of our clinical
    trials.
         46




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##### Table of Contents



If the
    contract manufacturers upon whom we rely fail to produce our
    product candidates in the volumes that we require on a timely
    basis, or fail to comply with stringent regulations applicable
    to pharmaceutical drug manufacturers, we may face delays in the
    development and commercialization of our product
    candidates.
         47




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##### Table of Contents



Bupropion,
    which is an API in both Contrave and Empatic, is known to have
    issues with stability.
    We
    face potential product liability exposure, and, if successful
    claims are brought against us, we may incur substantial
    liability.
    
    decreased demand for our product candidates;
    impairment of our business reputation;
    withdrawal of clinical trial participants;
    costs of related litigation;
    distraction of managements attention from our primary
    business;
    substantial monetary awards to patients or other claimants;
    loss of revenues; and
    the inability to commercialize our product candidates.    If any
    of our product candidates for which we receive regulatory
    approval does not achieve broad market acceptance, the revenues
    that we generate from their sales will be limited.
    
    our ability to provide acceptable evidence of safety and
    efficacy;
    the relative convenience and ease of administration;
    the prevalence and severity of any adverse side effects; 48




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
    limitations or warnings contained in a products
    FDA-approved labeling, including, for example, potential
    black box warnings or pregnancy precautions
    associated with the APIs in Contrave
    and/or
    Empatic;
    availability of alternative treatments, including, in the case
    of Contrave
    and/or
    Empatic, a number of competitive products already approved for
    the treatment of weight loss or expected to be commercially
    launched in the near future;
    pricing and cost effectiveness;
    the effectiveness of our or any future collaborators sales
    and marketing strategies;
    our ability to obtain sufficient third-party coverage or
    reimbursement; and
    the willingness of patients to pay out of pocket in the absence
    of third-party coverage.    We are
    subject to uncertainty relating to reimbursement policies which,
    if not favorable to our product candidates, could hinder or
    prevent our product candidates commercial
    success.
      out-of-pocket
    Our
    failure to successfully acquire, develop and market additional
    product candidates or approved products would impair our ability
    to grow.
  and/or
 49




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
    exposure to unknown liabilities;
    disruption of our business and diversion of our
    managements time and attention to develop acquired
    products or technologies;
    incurrence of substantial debt or dilutive issuances of
    securities to pay for acquisitions;
    higher than expected acquisition and integration costs;
    increased amortization expenses;
    difficulty and cost in combining the operations and personnel of
    any acquired businesses with our operations and personnel;
    impairment of relationships with key suppliers or customers of
    any acquired businesses due to changes in management and
    ownership; and
    inability to retain key employees of any acquired businesses.    Healthcare
    reform measures could hinder or prevent our product
    candidates commercial success.
      
    our ability to set a price we believe is fair for our products;
    our ability to generate revenues and achieve or maintain
    profitability; and
    the availability of capital. 50




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We
    will need to increase the size of our organization, and we may
    experience difficulties in managing growth.
    
    manage our clinical trials effectively, including our ongoing
    Phase III clinical trials for Contrave which are being
    conducted at numerous clinical trial sites and our upcoming
    Phase II clinical trial for Empatic;
    manage the manufacturing and development of Contrave and Empatic;
    manage our internal development efforts effectively while
    carrying out our contractual obligations to licensors,
    contractors, collaborators and other third parties;
    continue to improve our operational, financial and management
    controls, reporting systems and procedures; and
    attract and retain the breadth and depth of sufficient numbers
    of talented employees.    We may
    not be able to manage our business effectively if we are unable
    to attract and retain key personnel.
       51




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##### Table of Contents



We
    will need to obtain FDA approval of our proposed product names,
    Contrave and Empatic, and any failure or delay associated with
    such approval may adversely impact our business.
  and/or
  If we
    fail to comply with healthcare regulations, we could face
    substantial penalties and our business, operations and financial
    condition could be adversely affected.
    
    the federal healthcare program Anti-Kickback Law, which
    prohibits, among other things, persons from soliciting,
    receiving or providing remuneration, directly or indirectly, to
    induce either the referral of an individual, for an item or
    service or the purchasing or ordering of a good or service, for
    which payment may be made under federal healthcare programs such
    as the Medicare and Medicaid programs;
    federal false claims laws which prohibit, among other things,
    individuals or entities from knowingly presenting, or causing to
    be presented, claims for payment from Medicare, Medicaid, or
    other third-party payors that are false or fraudulent, and which
    may apply to entities like us which provide coding and billing
    advice to customers;
    the federal Health Insurance Portability and Accountability Act
    of 1996, or HIPAA, which prohibits executing a scheme to defraud
    any healthcare benefit program or making false statements
    relating to healthcare matters and which also imposes certain
    requirements relating to the privacy, security and transmission
    of individually identifiable health information;
    the Federal Food, Drug, and Cosmetic Act, which among other
    things, strictly regulates drug product marketing, prohibits
    manufacturers from marketing drug products for off-label use and
    regulates the distribution of drug samples; and
    state law equivalents of each of the above federal laws, such as
    anti-kickback and false claims laws which may apply to items or
    services reimbursed by any third-party payor, including
    commercial insurers, and state laws governing the privacy and
    security of health information in certain circumstances, many of
    which differ from each other in significant ways and often are
    not preempted by HIPAA, thus complicating compliance efforts. 52




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Our
    business involves the use of hazardous materials and we and our
    third-party manufacturers must comply with environmental laws
    and regulations, which can be expensive and restrict how we do
    business.
    Our
    business and operations would suffer in the event of system
    failures.
    Risks
    Related to Intellectual Property
  The
    issued patent rights that we have in-licensed covering Contrave
    and Empatic are limited to the United States and although we
    have international patent applications pending, our market
    opportunity for Contrave and Empatic may be limited by the lack
    of patent protection in other territories. In addition, although
    we have additional U.S. and international patent applications
    pending which seek further protection of all of our product
    candidates, these applications may not issue on a timely basis
    or at all.
   53




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54




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Even
    if the international patent applications for our product
    candidates issue or receive approval, we may face additional
    competition outside of the United States as a result of a lack
    of patent enforcement in foreign countries and off-label use of
    other dosage forms of the generic components in our product
    candidates.
     55




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We
    have in-licensed all or a portion of the rights to our product
    candidates from third parties. If we default on any of our
    material obligations under those licenses, we could lose rights
    to our product candidates.
    Restrictions
    on our patent rights relating to our product candidates may
    limit our ability to prevent third parties from competing
    against us.
           56




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If we
    are sued for infringing intellectual property rights of third
    parties, it will be costly and time consuming, and an
    unfavorable outcome in that litigation would have a material
    adverse effect on our business.
  and/or
  and/or
    
    infringement and other intellectual property claims which,
    regardless of merit, may be expensive and time-consuming to
    litigate and may divert our managements attention from our
    core business;
    substantial damages for infringement, which we may have to pay
    if a court decides that the product at issue infringes on or
    violates the third partys rights, and if the court finds
    that the infringement was willful, we could be ordered to pay
    treble damages and the patent owners attorneys fees;
    a court prohibiting us from selling or licensing the product
    unless the third party licenses its product rights to us, which
    it is not required to do;
    if a license is available from a third party, we may have to pay
    substantial royalties and fees
    and/or grant
    cross-licenses to intellectual property rights for our
    products; and
    redesigning our products or processes so they do not infringe,
    which may not be possible or may require substantial monetary
    expenditures and time.  and/or
 57




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and/or
    Although
    we have entered into a settlement agreement designed to prevent
    the parties to the agreement from asserting infringement and
    other specified claims against our Empatic product candidate in
    the United States, and abroad, disputes with third parties
    relating to our Empatic product could nevertheless affect our
    intellectual property rights.
       58




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and/or
  Obtaining
    and maintaining our patent protection depends on compliance with
    various procedural, document submission, fee payment and other
    requirements imposed by governmental patent agencies, and our
    patent protection could be reduced or eliminated for
    non-compliance with these requirements.
    We
    have not yet registered our trademarks in all of our potential
    markets, and failure to secure those registrations could
    adversely affect our business.
  intent-to-use
 59




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intent-to-use
  We may
    be subject to claims that our employees have wrongfully used or
    disclosed alleged trade secrets of their former
    employers.
    Risks
    Related to Our Finances and Capital Requirements
  We
    have incurred significant operating losses since our inception
    and anticipate that we will incur continued losses for the
    foreseeable future.
   60




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We
    have not generated any revenue from our product candidates and
    may never be profitable.
    
    successfully complete our ongoing and planned clinical trials
    for Contrave and Empatic;
    obtain regulatory approval for Contrave and Empatic;
    manufacture commercial quantities of our product candidates at
    acceptable cost levels if regulatory approvals are
    received; and
    identify and enter into one or more strategic collaborations to
    effectively market and sell our product candidates.    Our
    short operating history makes it difficult to evaluate our
    business and prospects.
    We
    will need additional funding and may be unable to raise capital
    when needed, which would force us to delay, reduce or eliminate
    our product development programs or commercialization
    efforts.
  proof-of-concept
  
    fund our operations and continue to conduct clinical trials to
    support potential regulatory approval of marketing applications;
    qualify and outsource the commercial-scale manufacturing of our
    products under cGMPs; and
    commercialize Contrave, Empatic or any other product candidates
    that we may develop, in-license or acquire, if any of these
    product candidates receive regulatory approval.    
    the rate of progress and cost of our clinical trials and other
    product development programs for Contrave, Empatic and any other
    product candidates that we may develop, in-license or acquire;
    the costs of filing, prosecuting, defending and enforcing any
    patent claims and other intellectual property rights associated
    with our product candidates; 61




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
    the costs and timing of completion of outsourced commercial
    manufacturing supply arrangements for each product candidate;
    the timing of regulatory approval of our product candidates, if
    at all;
    the costs of establishing sales, marketing and distribution
    capabilities, should we elect to do so;
    the effect of competing technological and market
    developments; and
    the terms and timing of any collaborative, licensing,
    co-promotion or other arrangements that we may establish.      Our
    quarterly operating results may fluctuate
    significantly.
    
    variations in the level of expenses related to our two existing
    product candidates or future development programs;
    addition or termination of clinical trials or funding support;
    any intellectual property infringement lawsuit in which we may
    become involved;
    regulatory developments affecting our product candidates or
    those of our competitors;
    our execution of any collaborative, licensing or similar
    arrangements, and the timing of payments we may make or receive
    under these arrangements; and
    if any of our product candidates receives regulatory approval,
    the level of underlying demand for our product candidates and
    wholesalers buying patterns.    Raising
    additional funds by issuing securities may cause dilution to
    existing stockholders and raising funds through lending and
    licensing arrangements may restrict our operations or require us
    to relinquish proprietary rights.
   62




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We
    incur significant costs as a result of operating as a public
    company, and our management is required to devote substantial
    time to public company compliance initiatives.
      Risks
    Relating to Securities Markets and Investment in Our
    Stock
  The
    market price of our common stock has fluctuated and is likely to
    continue to fluctuate, which could reduce the market price of
    our common stock.
   63




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
    the results from our clinical trials, including our current
    Phase III clinical trials for Contrave and our upcoming
    Phase II clinical trial for Empatic;
    FDA or international regulatory actions, including failure to
    receive regulatory approval for any of our product candidates;
    announcements regarding manufacturing or supply developments for
    Contrave or Empatic;
    failure of any of our product candidates, if approved, to
    achieve commercial success;
    announcements of the introduction of new products by us or our
    competitors;
    market conditions in the pharmaceutical and biotechnology
    sectors;
    announcements concerning product development results or
    intellectual property rights of others;
    litigation or public concern about the safety of our potential
    products;
    actual and anticipated fluctuations in our quarterly operating
    results;
    deviations in our operating results from the estimates of
    securities analysts or other analyst comments;
    additions or departures of key personnel;
    third-party coverage and reimbursement policies;
    developments concerning current or future strategic
    collaborations; and
    discussion of us or our stock price by the financial and
    scientific press and in online investor communities.    Future
    sales of our common stock may depress our stock
    price.
  Rule 10b5-1
  Rule 10b5-1
  Our
    executive officers and directors and their affiliates will
    exercise significant influence over stockholder voting matters
    in a manner that may not be in the best interests of all of our
    stockholders.
   64




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Anti-takeover
    provisions under our charter documents and Delaware law could
    delay or prevent a change of control which could limit the
    market price of our common stock and may prevent or frustrate
    attempts by our stockholders to replace or remove our current
    management.
    
    a board of directors divided into three classes serving
    staggered three-year terms, such that not all members of the
    board will be elected at one time;
    a prohibition on stockholder action through written consent;
    a requirement that special meetings of stockholders be called
    only by the chairman of the board of directors, the chief
    executive officer, the president or by a majority of the total
    number of authorized directors;
    advance notice requirements for stockholder proposals and
    nominations;
    a requirement of approval of not less than
    662/3%
    of all outstanding shares of our capital stock entitled to vote
    to amend any bylaws by stockholder action, or to amend specific
    provisions of our certificate of incorporation; and
    the authority of the board of directors to issue preferred stock
    on terms determined by the board of directors without
    stockholder approval.    We
    have never paid dividends on our capital stock, and because we
    do not anticipate paying any cash dividends in the foreseeable
    future, capital appreciation, if any, of our common stock will
    be your sole source of gain on an investment in our
    stock.
    We may
    become involved in securities class action litigation that could
    divert managements attention and harm our
    business.
   65




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Item 1B.
    Unresolved
    Staff Comments.    Item 2.
    Properties.    Item 3.
    Legal
    Proceedings.       66




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##### Table of Contents



and/or
    Item 4.
    Submission
    of Matters to a Vote of Security Holders.   PART II  Item 5.
    Market
    for Registrants Common Equity, Related Stockholder Matters
    and Issuer Purchases of Equity Securities.  Market
    Information
      High


LowYear Ended December 31, 2007:Fourth Quarter

$
18.45


$
12.83Third Quarter


17.86



12.83Second Quarter (beginning April 26, 2007)


19.15



12.50First Quarter


N/A



N/A    67




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Dividend
    Policy
    Use of
    Proceeds
  Form S-1 No. 333-139496) No. 333-142375).
    tm tm
  Equity
    Compensation Plan Information
    Number ofShares Issuable


Weighted


SecuritiesUpon Exercise


Average


Available forof Outstanding


Exercise


FutureAwards


Price


IssuanceEquity compensation plans approved by security holders:2004 Stock Plan


2,279,730


$
1.48



2007 Equity Incentive Award Plan


593,632


$
14.63



3,634,608    68




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##### Table of Contents



Comparative
    Stock Performance Graph
  The information contained in this Stock Performance Graph
    section shall not be deemed to be soliciting
    material or filed with the SEC or subject to
    the liabilities of section 18 of the Exchange Act unless we
    specifically incorporate it by reference into a document filed
    under the Securities Act or the Exchange Act.
    
  April 26, 2007


December 31, 2007Orexigen Therapeutics, Inc.


$
100



$
109.6Nasdaq Composite Index


$
100



$
103.8Nasdaq Biotechnology Index


$
100



$
97.3   Sales of
    Unregistered Securities
    Repurchases
    of Equity Securities
   69




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Item 6.
    Selected
    Financial Data    Period FromSeptember 12, 2002Years Ended December 31,


(Inception) to2007


2006


2005


2004


2003


December 31, 2007(In thousands, except per share amounts)Statement of Operations Data:Revenues:Collaborative agreement

$



$



$
174


$



$



$
174License revenue


88



88



88











265Total revenues


88



88



262











439Operating expenses:Research and development


50,253



22,586



9,709



6,145



1,164



89,857General and administrative


10,657



5,870



3,386



1,590



667



22,171Total operating expenses


60,910



28,456



13,095



7,735



1,831



112,028Loss from operations


(60,822
)


(28,368
)


(12,833
)


(7,735
)


(1,831
)


(111,589
)Other income (expense):Interest income


3,901



872



744



47







5,564Interest expense


(846
)


(8
)






(5
)


(50
)


(910
)Total other income (expense)


3,055



864



744



42



(50
)


4,654Net loss


(57,767
)


(27,504
)


(12,089
)


(7,693
)


(1,881
)


(106,935
)Accretion to redemption value of redeemable convertible
    preferred stock


(10
)


(31
)


(24
)


(13
)






(78
)Deemed dividend of beneficial conversion for Series C
    preferred stock






(13,860
)














(13,860
)Net loss attributable to common stockholders

$
(57,777
)

$
(41,395
)

$
(12,113
)

$
(7,706
)

$
(1,881
)

$
(120,873
)Basic and diluted net loss per share(1)

$
(3.08
)

$
(18.87
)

$
(6.12
)

$
(5.01
)

$
(2.31
)Shares used to calculate net loss per share(1)


18,757



2,193


$
1,980



1,539



814     (1)
    
    See Note 2 of Notes to Financial Statements for an
    explanation of the method used to calculate the net loss per
    share and the number of shares used in the computation of the
    per share amounts.  As of December 31,2007


2006


2005


2004


2003(In thousands)Balance Sheet Data:Cash and cash equivalents and investment securities,
    available-for-sale

$
85,454


$
34,413


$
27,647


$
1,674


$
19Working capital (deficit)


74,648



29,644



26,412



1,318



(188
)Total assets


91,320



36,810



28,114



1,750



46Long-term debt, less current portion


11,072















Redeemable convertible preferred stock






45,897



45,866



10,928



Deficit accumulated during the development stage


(106,935
)


(49,168
)


(21,664
)


(9,576
)


(1,882
)Total stockholders equity (deficit)


64,883



(15,847
)


(20,576
)


(9,537
)


(1,877
)  70




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Item 7.
    Managements
    Discussion And Analysis Of Financial Condition And Results Of
    Operations  The following discussion and analysis of our financial
    condition and results of operations should be read in
    conjunction with Item 6  Selected
    Financial Data and our financial statements and related
    notes appearing elsewhere in this annual report. In addition to
    historical information, this discussion and analysis contains
    forward-looking statements that involve risks, uncertainties and
    assumptions. Our actual results may differ materially from those
    anticipated in these forward-looking statements as a result of
    certain factors, including but not limited to those set forth
    under Item 1A  Risk Factors and
    elsewhere in this annual report.
  Overview
  Background
            Revenues
   71




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Research
    and Development Expenses
        Costs of external service providers:Obesity

$
44,514Non-Obesity


554Other


737Subtotal


45,805Internal costs


2,734Stock-based compensation


1,714Total research and development costs

$
50,253      72




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General
    and Administrative
    Other
    Income (Expense)
    Income
    Taxes
    Beneficial
    Conversion Feature
  No. 98-5, Accounting for Convertible Securities with Beneficial
    Conversion Features
  Critical
    Accounting Policies and Estimates
   73




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Research
    and Development Expenses
    Stock-Based
    Compensation
  Share-Based Payment Accounting for Stock-Based
    Compensation Accounting for Stock Issued to
    Employees
           74




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96-18, Accounting for Equity Instruments That are Issued to Other
    Than Employees for Acquiring, or in Conjunction with Selling
    Goods and Services
  Income
    Taxes
  Accounting for Uncertainty in Income Taxes  An
    Interpretation of FASB Statement No. 109 Accounting for Income Taxes,
  Results
    of Operations
  Comparison
    of year ended December 31, 2007 to year ended
    December 31, 2006
  Revenues.
  Research and Development Expenses.
  General and Administrative Expenses.
  Interest and Other Income.
  Interest Expense.
 75




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Comparison
    of year ended December 31, 2006 to year ended
    December 31, 2005
  Revenues.
  Research and Development Expenses.
  General and Administrative Expenses.
  Interest and Other Income.
  Interest Expense.
  Comparison
    of year ended December 31, 2005 to year ended
    December 31, 2004
  Revenues.
  Research and Development Expenses.
  General and Administrative Expenses.
  Interest and Other Income.
 76




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Liquidity
    and Capital Resources
    
    from September 12, 2002 to December 31, 2006, we
    issued and sold a total of 1,053,572 shares of common stock
    for aggregate net proceeds of $14,801;
    in March 2004, we issued and sold a total of
    9,322,035 shares of Series A redeemable convertible
    preferred stock for aggregate net proceeds of $9.2 million
    and the conversion of promissory notes and interest thereon
    totaling $1.7 million;
    from April 2005 to May 2005, we issued and sold
    14,830,509 shares of Series B redeemable convertible
    preferred stock for aggregate net proceeds of $34.9 million;
    in November 2006, we issued and sold a total of
    8,771,930 shares of Series C convertible preferred
    stock for aggregate net proceeds of $29.9 million; and
    in May 2007, we issued and sold a total of 8,050,000 shares
    of common stock for aggregate net proceeds of $87.9 million.             77




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
    the progress of our clinical trials, including expenses to
    support the trials and milestone payments that may become
    payable;
    our ability to establish and maintain strategic collaborations,
    including licensing and other arrangements;
    the costs involved in enforcing or defending patent claims or
    other intellectual property rights;
    the costs and timing of regulatory approvals;
    the costs of establishing sales or distribution capabilities;
    the successful commercialization of our products; and
    the extent to which we in-license, acquire or invest in other
    indications, products, technologies and businesses.         78




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Contractual
    Obligations and Commitments
    Payments Due by PeriodsTotal


Less Than 1 Year


1-3 Years


4-5 Years


AfterLong-term debt obligations(1)

$
15,807


$
4,735


$
10,072


$
1,000


$
Long-term liabilities(2)


941







920



21



Operating lease obligations


6,476



572



2,640



2,544



720License obligations(3)


















Total

$
23,224


$
5,307


$
13,632


$
3,565


$
720     (1)
    
    In December 2006, we entered into a credit and security
    agreement with Merrill Lynch Capital providing for the potential
    borrowing of up to $17.0 million. In November 2007, the
    amount available for borrowing under the credit and security
    agreement was increased to $25.0 million. In March and
    December 2007, we drew down $10.0 million and
    $8.0 million, respectively, under the credit and security
    agreement.(2)
    
    Primarily represents fees due to the lender incurred in
    connection with our credit and security agreement with Merrill
    Lynch Capital due on the earlier of the repayment of total
    amounts borrowed or termination of the agreement.(3)
    
    License obligations do not include additional payments of up to
    $2.7 million due upon the occurrence of certain milestones
    related to regulatory or commercial events or potential payments
    of up to $5.7 million to Duke University should we receive
    milestone payments from Cypress under our agreement with Cypress
    (up to $3.7 million excluding milestone payments unrelated
    to sleep apnea). We may also be required to pay royalties on any
    net sales of the licensed products. License payments may be
    increased based on the timing of various milestones and the
    extent to which the licensed technologies are pursued for other
    indications. These milestone payments and royalty payments under
    our license agreements are not included in the table above
    because we cannot, at this time, determine when or if the
    related milestones will be achieved or the events triggering the
    commencement of payment obligations will occur.    Recent
    Accounting Pronouncements
  Accounting for the
    Uncertainty in Income Taxes  an Interpretation of
    FASB Statement No. 109
  Fair Value Measurements
 79




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The
    Fair Value Option for Financial Assets and Financial
    Liabilities  including an Amendment of FASB Statement
    No. 115 instrument-by-instrument
  EITF 07-3, Accounting for Nonrefundable Advance Payments for Goods or
    Services to Be Used in Future Research and Development
    Activities EITF 07-3. EITF 07-3 EITF 07-3 EITF 07-3
  Off-Balance
    Sheet Arrangements
    Item 7A.
    Quantitative
    and Qualitative Disclosures About Market Risk   80




---



##### 



Item 8.
    Financial
    Statements and Supplementary Data  Index to
    Financial Statements
   
 PageNumberReport of Independent Registered Public
    Accounting Firm


82Balance Sheets


83Statements of Operations


84Statements of Redeemable Convertible Preferred
    Stock and Stockholders Equity (Deficit)


85Statements of Cash Flows


87Notes to Financial Statements


88   81




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##### Table of Contents



REPORT OF
    INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM  
        Share-Based Payment
  
    82




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
 BALANCE
    SHEETS
    (In thousands, except share and par value amounts)  December 31,2007


2006ASSETSCurrent assets:Cash and cash equivalents

$
28,967


$
19,425Investment securities, available-for-sale


56,487



14,988Prepaid expenses and other current assets


2,471



222Total current assets


87,925



34,635Property and equipment, net


924



528Restricted cash


1,125



155Other assets


1,346



1,492Total assets

$
91,320


$
36,810LIABILITIES AND STOCKHOLDERS EQUITY (DEFICIT)Current liabilities:Accounts payable

$
4,114


$
1,699Accrued expenses


4,340



3,204Deferred revenue, current portion


88



88Long-term debt, current portion


4,735



Total current liabilities


13,277



4,991Deferred revenue, less current portion


1,147



1,235Long-term debt, less current portion


11,072



Other long-term liabilities


941



534Commitments and contingenciesSeries A and B redeemable convertible preferred stock,
    $.001 par value, no shares authorized, issued and
    outstanding at December 31, 2007 and 24,152,544 shares
    authorized, issued and outstanding at December 31, 2006;
    aggregate liquidation preference of $46,000 at December 31,
    2006






45,897Stockholders equity (deficit):Preferred stock,$.001 par value, 10,000,000 shares
    authorized at December 31, 2007 and no shares authorized at
    December 31, 2006; no shares issued and outstanding at
    December 31, 2007






Series C convertible stock, $.001 par value, no shares
    authorized, issued or outstanding at December 31, 2007 and
    8,771,930 shares authorized, issued and outstanding at
    December 31, 2006; aggregate liquidation preference of
    $30,000 at December 31, 2006






9Common stock, $.001 par value, 100,000,000 shares
    authorized at December 31, 2007 and 50,000,000 shares
    authorized at December 31, 2006; 26,982,601 and
    2,398,039 shares issued and outstanding at
    December 31, 2007 and 2006, respectively


27



2Additional paid-in capital


171,571



33,299Accumulated other comprehensive income


220



11Deficit accumulated during the development stage


(106,935
)


(49,168
)Total stockholders equity (deficit)


64,883



(15,847
)Total liabilities and stockholders equity (deficit)

$
91,320


$
36,810    83




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OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
 STATEMENTS
    OF OPERATIONS
    (In thousands, except per share amounts)  Period fromSeptember 12,2002(Inception) toYears Ended December 31,


December 31,2007


2006


2005


2007Revenues:Collaborative agreement

$



$



$
174


$
174License revenue


88



88



88



265Total revenues


88



88



262



439Operating expenses:Research and development


50,253



22,586



9,709



89,857General and administrative


10,657



5,870



3,386



22,171Total operating expenses


60,910



28,456



13,095



112,028Loss from operations


(60,822
)


(28,368
)


(12,833
)


(111,589
)Other income (expense):Interest income


3,901



872



744



5,564Interest expense


(846
)


(8
)






(910
)Total other income (expense)


3,055



864



744



4,654Net loss


(57,767
)


(27,504
)


(12,089
)


(106,935
)Accretion to redemption value of redeemable convertible
    preferred stock


(10
)


(31
)


(24
)


(78
)Deemed dividend of beneficial conversion for Series C
    preferred stock






(13,860
)






(13,860
)Net loss attributable to common stockholders

$
(57,777
)

$
(41,395
)

$
(12,113
)

$
(120,873
)Net loss per share attributable to common
    stockholders  basic and diluted(1)

$
(3.08
)

$
(18.87
)

$
(6.12
)Shares used to compute basic and diluted net loss per share
    attributable to common stockholders(1)


18,757



2,193



1,980     (1)
    
    As a result of the issuance of 8,050,000 shares of common
    stock in the Companys initial public offering in May 2007
    and the conversion of the Companys preferred stock into
    16,462,231 shares of common stock upon completion of the
    Companys initial public offering, there is a lack of
    comparability in the basic and diluted net loss per share
    amounts for the periods presented. See Note 2 for further
    discussion.   84




---



##### Table of Contents






OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
 STATEMENTS
    OF REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS
    EQUITY (DEFICIT)
    PERIOD FROM SEPTEMBER 12, 2002 (INCEPTION) TO DECEMBER 31,
    2007
    (In thousands, except per share amounts)  DeficitAccumulated


Accumulated


TotalSeries A Redeemable


Series B Redeemable









Series C Convertible


Additional





Other


During the


StockholdersConvertible Preferred Stock


Convertible Preferred Stock



Common Stock


Preferred Stock


Paid-In


Deferred


Comprehensive


Development


EquityShares


Amount


Shares


Amount



Shares


Amount


Shares


Amount


Capital


Compensation


Income (Loss)


Stage


(Deficit)Balance at September 12, 2002 (inception)





$







$








$







$



$



$



$



$



$
Issuance of common stock to founder at $0.002 per share in
    exchange for services in September



















650



1



























1Net loss and comprehensive loss















































(1
)


(1
)Balance at December 31, 2002



















650



1























(1
)


Issuance of common stock at $0.002 per share for cash in June,
    November and December



















949



1











1















2Issuance of common stock at $0.002 per share in exchange for
    services in December



















443















1















1Issuance of common stock at $0.002 per share in exchange for
    technology in December



















76































Issuance of common stock options to consultant in exchange for
    services



































1















1Net loss and comprehensive loss















































(1,881
)


(1,881
)Balance at December 31, 2003



















2,118



2











3











(1,882
)


(1,877
)Issuance of Series A redeemable convertible preferred stock
    at $1.18 per share for cash in January, net of issuance costs


7,864



9,194












































Issuance of Series A redeemable convertible preferred stock
    for conversion of notes payable and accrued interest in January


1,458



1,721












































Issuance of common stock at $0.002 per share in exchange for
    technology in March



















443















44















44Issuance of common stock options to consultants in exchange for
    services in March



































2















2Accretion of redeemable convertible preferred stock to
    redemption value






13




























(13
)














(13
)Net loss and comprehensive loss















































(7,693
)


(7,693
)Balance at December 31, 2004


9,322



10,928












2,561



2











36











(9,575
)


(9,537
)Deferred employee stock based compensation related to issuance
    of stock options to employees



































5,029



(5,029
)










Amortization of deferred compensation







































1,113











1,113Stock-based compensation for common stock issued to consultants
    in exchange for services



































2















2Repurchase of common stock at $0.002 per share for cash in
    January



















(267
)






























Exercise of common stock options at $0.10 per share for cash



















59















6















6Issuance of Series B redeemable convertible preferred stock
    for cash at $2.36 per share in April and May, net of issuance
    costs










14,831



34,915




































  85




---



##### Table of Contents






OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  STATEMENTS
    OF REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS
    EQUITY
    (DEFICIT)
    (Continued)
  DeficitAccumulated


Accumulated


TotalSeries A Redeemable


Series B Redeemable









Series C Convertible


Additional





Other


During the


StockholdersConvertible Preferred Stock


Convertible Preferred Stock



Common Stock


Preferred Stock


Paid-In


Deferred


Comprehensive


Development


EquityShares


Amount


Shares


Amount



Shares


Amount


Shares


Amount


Capital


Compensation


Income (Loss)


Stage


(Deficit)Accretion of redeemable convertible preferred stock to
    redemption value






13







10




















(24
)














(24
)Comprehensive loss:Unrealized loss on securities, available-for-sale











































(47
)






(47
)Net loss















































(12,089
)


(12,089
)Total comprehensive loss



















































(12,136
)Balance at December 31, 2005


9,322



10,941



14,831



34,925




2,353



2











5,049



(3,916
)


(47
)


(21,664
)


(20,576
)Reversal of deferred compensation upon adoption of
    FAS 123(R)



































(3,916
)


3,916











Exercise of common stock options at $0.10 and $0.60 per share
    for cash



















45















7















7Stock-based compensation expense



































2,258















2,258Accretion of redeemable convertible preferred stock to
    redemption value






14







17




















(31
)














(31
)Issuance of Series C convertible preferred stock for cash
    at $3.42 per share in November, net of issuance costs



























8,772



9



29,932















29,941Beneficial conversion feature  deemed dividend on
    issuance of Series C convertible preferred stock



































13,860















13,860Beneficial conversion feature  deemed dividend of
    beneficial conversion feature for Series C convertible
    preferred stock



































(13,860
)














(13,860
)Comprehensive loss:Unrealized loss on securities, available-for-sale











































58







58Net loss















































(27,504
)


(27,504
)Total comprehensive loss



















































(27,446
)Balance at December 31, 2006


9,322



10,955



14,831



34,942




2,398



2



8,772



9



33,299







11



(49,168
)


(15,847
)Accretion of redeemable convertible preferred stock to
    redemption value






4







6




















(10
)














(10
)Issuance of common stock in initial public offering at $12.00
    per share, net of issuance costs



















8,050



8











87,883















87,891Conversion of preferred stock in connection with initial public
    offering


(9,322
)


(10,959
)


(14,831
)


(34,948
)



16,462



17



(8,772
)


(9
)


45,899















45,907Exercise of common stock options at $0.10, $0.60, $0.70 and
    $2.00 per share for cash



















73















77















77Stock-based compensation expense



































4,423















4,423Comprehensive loss:Unrealized loss on securities, available-for-sale











































209







209Net loss















































(57,767
)


(57,767
)Total comprehensive loss



















































(57,558
)Balance at December 31, 2007





$







$





26,983


$
27






$



$
171,571


$



$
220


$
(106,935
)

$
64,883    86




---



##### Table of Contents





OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
 STATEMENTS
    OF CASH FLOWS
    (In thousands)  Period fromSeptember 12,2002(Inception) toYears Ended December 31,


December 31,2007


2006


2005


2007Operating activitiesNet loss

$
(57,767
)

$
(27,504
)

$
(12,089
)

$
(106,935
)Adjustments to reconcile net loss to net cash used in operating
    activities:Amortization of premium (discount) on investment securities,
    available-for-sale


(2,476
)


74



33



(2,368
)Amortization of debt issuance costs


203



8







211Depreciation


138



44



9



195Loss on disposal of fixed assets










4



4Issuance of common stock in exchange for technology and services














47Stock-based compensation


4,423



2,258



1,115



7,799Changes in operating assets and liabilities:Prepaid expenses and other current assets


(2,249
)


43



(262
)


(2,471
)Accounts payable and accrued expenses


3,551



3,490



1,053



8,509Other assets


(130
)


(167
)


9



(324
)Deferred rent


7



34







41Deferred revenue


(88
)


(88
)


1,412



1,235Net cash used in operating activities


(54,388
)


(21,808
)


(8,716
)


(94,057
)Investing activitiesPurchases of investment securities, available-for-sale


(134,814
)


(21,447
)


(34,687
)


(190,949
)Maturities and sales of investment securities, available-for-sale


96,000



25,351



15,700



137,051Purchases of property and equipment


(534
)


(427
)


(151
)


(1,123
)Restricted cash


(970
)


(125
)






(1,125
)Net cash provided by (used in) investing activities


(40,318
)


3,352



(19,138
)


(56,146
)Financing activitiesProceeds from borrowings of long-term debt


18,000











18,000Payments on borrowings on long-term debt


(2,193
)










(2,193
)Proceeds from issuance of redeemable convertible preferred stock
    for cash, net of issuance costs










34,915



44,109Proceeds from issuance of convertible preferred stock for cash,
    net of issuance costs






29,940







29,940Proceeds from promissory notes














1,665Costs paid in connection with loan agreement


(43
)


(183
)






(226
)Costs paid in connection with initial public offering


623



(623
)






Proceeds from issuance of common stock, net of repurchases


87,968



7



5



87,982Costs paid in connection with public offering


(107
)










(107
)Net cash provided by financing activities


104,248



29,141



34,920



179,170Increase (decrease) in cash and cash equivalents


9,542



10,685



7,066



28,967Cash and cash equivalents at beginning of period


19,425



8,740



1,674



Cash and cash equivalents at end of period

$
28,967


$
19,425


$
8,740


$
28,967Supplemental DisclosureInterest paid

$
581


$



$



$
581Unrealized gain (loss) on investment securities,
    available-for-sale

$
209


$
58


$
(47
)

$
220Non-cash financing activitiesConversion of notes payable and accrued interest to redeemable
    convertible preferred stock

$



$



$



$
1,721Accretion to redemption value of redeemable convertible
    preferred stock

$
10


$
31


$
24


$
78    87




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
 NOTES TO
    FINANCIAL STATEMENTS 1.
    Organization
    and Basis of Presentation      2.
    Summary
    of Significant Accounting Policies  Initial
    Public Offering
    Use of
    Estimates
    Cash
    and Cash Equivalents
    Investment
    Securities, Available-for-Sale
   88




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  Restricted
    Cash
    Fair
    Value of Financial Instruments
    Concentration
    of Credit Risk
    Concentration
    of Revenue
    Property
    and Equipment
    Impairment
    of Long-Lived Assets
  Accounting for the
    Impairment of Disposable Long-Lived Assets
  Research
    and Development Costs
   89




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Patent
    Costs
    Income
    Taxes
  Accounting for Income Taxes
  Revenue
    Recognition
  Revenue Recognition 00-21, Revenue Arrangements with Multiple Deliverables
      Stock-Based
    Compensation
  Accounting for Stock issued to Employees
 90




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  Accounting for Stock-Based
    Compensation
  Share-Based Payment
      Years EndedDecember 31,2007


2006Expected life (in years)


6.1



6.2Expected volatility


70.0
%


70.0
%Risk-free interest rate


4.1
%


4.7
%Expected dividend yield






    91




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
      Period fromSeptember 12,2002Years Ended


(Inception) toDecember 31,


December 31,2007


2006


2007General and administrative

$
2,709


$
1,649


$
5,263Research and development


1,714



609



2,536$
4,423


$
2,258


$
7,799     paid-in-capital.
  No. 96-18, Accounting for Equity Instruments That are Issued to Other
    Than Employees for Acquiring, or in Conjunction with Selling
    Goods and Services
  Comprehensive
    Income ( Loss)
  Reporting Comprehensive Income
  Net
    Loss Per Share
   92




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Years Ended December 31,2007


2006


2005(In thousands, except per share amounts)HistoricalNumerator:Net loss attributable to common stockholders

$
(57,777
)

$
(41,395
)

$
(12,113
)Denominator:Weighted average common shares outstanding


18,789



2,379



2,330Weighted average unvested common shares subject to repurchase


(32
)


(186
)


(350
)Denominator for basic and diluted net loss attributable to
    common stockholders


18,757



2,193



1,980Net loss attributable to common stockholders per
    share  basic and diluted

$
(3.08
)

$
(18.87
)

$
(6.12
)     As of December 31,2007


2006


2005Common stock options


2,873



2,297



1,339Common shares subject to repurchase






110



275Redeemable convertible preferred stock (as converted)






16,462



12,0762,873



18,869



13,690  93




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  Pro
    Forma Net Loss per Share
    Years Ended December 31,2007


2006


2005Numerator:Net loss attributable to common stockholders

$
(57,777
)

$
(41,395
)

$
(12,113
)Adjustment to eliminate accretion on preferred stock and
    beneficial conversion of series C preferred stock


10



13,891



24Pro forma net loss

$
(57,767
)

$
(27,504
)

$
(12,089
)Denominator:Weighted average shares of common stock outstanding


18,757



2,193



1,980Pro forma adjustment to reflect assumed conversion of preferred
    stock, as-if-converted


5,457



12,545



9,768Denominator for pro forma basic and diluted net loss per share


24,214



14,738



11,748Pro forma basic and diluted net loss per share

$
(2.39
)

$
(1.87
)

$
(1.03
)   New
    Accounting Standards Not Yet Adopted
  Fair Value Measurements
  The Fair Value Option for
    Financial Assets and Financial Liabilities
  EITF 07-3, Accounting for Nonrefundable Advance Payments for Goods or
    Services to Be Used in Future Research and Development
    Activities
    ( EITF 07-3). EITF 07-3 EITF 07-3 EITF 07-3
 94




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  3.
    Commitments
    and Contingencies  Credit
    and Security Agreement
        Due in:2008

$
4,7352009


6,0262010


4,0462011


1,00015,807Less current portion


(4,735
)$
11,072    95




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Operating
    Lease
        Years Ending December 31,2008

$
5722009


1,2982010


1,3422011


1,3462012


1,198Thereafter


720$
6,476     Technology
    and License Agreements
  Oregon
    Health & Science University
   96




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  in vitro
    and/or and/or
  Duke
    University
     97




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Lee
    Dante, M.D.
      Cypress
    Bioscience, Inc.
       98




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Eli
    Lilly and Company
    4.
    Investment
    Securities, Available-for-Sale    UnrealizedDecember 31, 2007

Maturity in Years

Amortized Cost


Gains


Losses


Fair ValueCorporate debt obligations

Less than 1

$
49,194


$
218


$
(2
)

$
49,410Corporate debt obligations

2-3


7,073



4







7,077Total investment securities



$
56,267


$
222


$
(2
)

$
56,487   UnrealizedDecember 31, 2006

Maturity in Years

Amortized Cost


Gains


Losses


Fair ValueCorporate debt obligations

Less than 1

$
31,820


$
11


$



$
31,831Corporate debt obligations

2-3


1,249











1,24933,069



11







33,080Less cash equivalents




(18,092
)










(18,092
)Amounts classified as investments



$
14,977


$
11


$



$
14,988  99




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  5.
    Property
    and Equipment    December 31,Useful Life in Years

2007


2006Furniture and fixtures

5

$
311


$
311Computer equipment

3 to 5


111



105Leasehold improvements

5


42



36Laboratory equipment




648



1261,112



578Accumulated depreciation




(188
)


(50
)Property and equipment, net



$
924


$
528   6.
    Accrued
    Expenses    December 31,2007


2006Accrued preclinical and clinical trial expenses

$
2,079


$
2,269Accrued compensation related expenses


1,760



762Accrued legal and professional expenses


87



104Other accrued expenses


414



69$
4,340


$
3,204   7.
    Redeemable
    Convertible Preferred Stock and Stockholders
    Equity  Redeemable
    Convertible Preferred Stock
       100




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
              Shares Authorized,


LiquidationIssued and


Preference andSeries

Outstanding


Redemption Value


Carrying ValueSeries A


9,322


$
11,000


$
10,955Series B


14,831



35,000



34,94224,153


$
46,000


$
45,897   Convertible
    Preferred Stock
  No. 98-5, Accounting for Convertible Securities with Beneficial
    Conversion Features
   101




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
      Common
    Stock
        Stock
    Options
     102




---



##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Number of


Weighted AverageOptions


Exercise PriceOutstanding at December 31, 2002 and 2003





$
Granted


223,624


$
0.10Outstanding at December 31, 2004


223,624


$
0.10Granted


1,260,683


$
0.54Exercised


(58,973
)

$
0.10Cancelled


(86,203
)

$
0.10Outstanding at December 31, 2005


1,339,131


$
0.52Granted


1,240,444


$
1.86Exercised


(45,000
)

$
0.16Cancelled


(237,513
)

$
0.60Outstanding at December 31, 2006


2,297,062


$
1.24Granted


648,632


$
14.29Exercised


(72,332
)

$
1.06Outstanding at December 31, 2007


2,873,362


$
4.19     Outstanding Options


Exercisable OptionsWeighted








WeightedAverage








AverageRemaining








RemainingNumber of


Contractual


Number of


Weighted


ContractualExercise

Outstanding


Life


Exercisable


Average


LifePrice

Options


(In Years)


Options


Exercise Price


(In Years)$0.10


177,403



7.0



177,403


$
0.10



7.0$0.60


840,883



7.4



674,216


$
0.60



7.4$0.70


254,944



8.5



254,944


$
0.70



8.5$2.00


909,000



8.8



272,177


$
2.00



8.8$6.00


42,500



8.9



11,510


$
6.00



8.9$10.72


55,000



9.1






$
10.72



$14.25


46,632



10.0






$
14.25



$14.26


272,000



10.0






$
14.26



$14.46


5,000



9.8






$
14.46



$14.59


72,000



9.6



1,302


$
14.59



9.6$14.82


68,000



9.9






$
14.82



$15.45


130,000



9.6






$
15.45



2,873,362



8.5



1,391,552


$
0.89



7.8    103




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
    Fair ValueEstimate per


IntrinsicNumber of


Exercise


Common


Value perDate of Issuance

Options Granted


Price


Share


Option ShareMay 2005


1,113,396


$
0.60


$
6.00


$
5.40May 2006


262,944


$
0.70


$
7.00


$
6.30September 2006


935,000


$
2.00


$
10.00


$
8.00November 2006


37,500


$
6.00


$
10.00


$
4.00         Weighted AverageGrant-Date FairShares


ValueNon vested outstanding at December 31, 2006


1,793,171


$
3.53Granted


648,632



9.16Vested


(666,766
)


3.26Non vested outstanding at December 31, 2007


1,775,037


$
5.69   Common
    Stock Reserved for Future Issuance
    Stock options issued and outstanding






2,873,362Authorized for future option grants






3,634,6086,507,970  104




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  8.
    Income
    Taxes    December 31,2007


2006(In thousands)Deferred tax assets:Net operating loss carryforwards

$
36,841


$
17,154Research and development credits


6,376



3,326Deferred revenue


503



539Other, net


461



245Total deferred tax assets


44,181



21,264Less valuation allowance


(44,181
)


(21,264
)$



$
      105




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  Accounting for Uncertainty in
    Income Taxes  An Interpretation of FASB Statement
    No. 109
  Balance at January 1, 2007

$
768Increases related to current year tax positions


1,110Balance at December 31, 2007

$
1,878       9.
    Litigation     106




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
        10.
    Related
    Party Transactions       107




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##### Table of Contents



OREXIGEN
    THERAPEUTICS, INC.
    (a development stage company)
  NOTES TO
    FINANCIAL STATEMENTS  (Continued)
  11.
    Employee
    Benefit Plan    12.
    Selected
    Quarterly Financial Data (Unaudited)    Year Ended December 31, 20071st Quarter


2nd Quarter


3rd Quarter


4th QuarterSelected quarterly financial data:Revenues

$
22


$
22


$
22


$
22Total operating expenses


12,489



12,496



15,632



20,293Net loss


(12,169
)


(11,630
)


(14,548
)


(19,420
)Net loss attributable to common stockholders


(12,177
)


(11,633
)


(14,548
)


(19,419
)Net loss per common stockholder  basic and diluted(1)


(5.26
)


(0.63
)


(0.54
)


(0.72
)   Year Ended December 31, 20061st Quarter


2nd Quarter


3rd Quarter


4th QuarterSelected quarterly financial data:Revenues

$
21


$
21


$
21


$
25Total operating expenses


5,503



5,631



7,619



9,703Net loss


(5,234
)


(5,384
)


(7,424
)


(9,462
)Net loss attributable to common stockholders


(5,242
)


(5,391
)


(7,431
)


(23,331
)Net loss per common stockholder  basic and diluted(1)


(2.49
)


(2.48
)


(3.34
)


(10.28
)     (1)
    
    Net loss per common stockholder is computed independently for
    each of the quarters presented. Therefore the sum of the
    quarterly net loss per share will no necessarily equal the total
    for the year.  13.
    Subsequent
    Events  Public
    Offering of Common Stock
   108




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##### Table of Contents



Item 9.
    Changes
    in and Disagreements with Accountants on Accounting and
    Financial Disclosure.    Item 9A.
    Controls
    and Procedures.  Evaluation
    of Disclosure Controls and Procedures
    Rule 13a-15(b),
    Item 9B.
    Other
    Information.   PART III  Form 10-K Form 10-K,
  Item 10.
    Directors,
    Executive Officers and Corporate Governance.    www.orexigen.com. Regulation S-K.
 109




---



##### 



Item 11.
    Executive
    Compensation.    Item 12.
    Security
    Ownership of Certain Beneficial Owners and Management and
    Related Stockholder Matters.    Item 13.
    Certain
    Relationships and Related Transactions, and Director
    Independence.    Item 14.
    Principal
    Accounting Fees and Services.   PART IV  Item 15.
    Exhibits,
    Financial Statement Schedules.       
 Page NumberBalance Sheets  December 31, 2007 and 2006


83Statements of Operations  Years Ended
    December 31, 2007, 2006 and 2005 and Period from Inception
    (September 12, 2002) to December 31, 2007


84Statements of Redeemable Convertible Preferred Stock and
    Stockholders Equity  Period from Inception
    (September 12, 2002) to December 31, 2007


85Statements of Cash Flows  Years Ended
    December 31, 2007, 2006 and 2005 and Period from Inception
    (September 12, 2002) to December 31, 2007


87Notes to Financial Statements


88      Regulation S-K.
 110




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##### Table of Contents



ExhibitNumber

Description3.1(1)

Amended and Restated Certificate of Incorporation of the
    Registrant3.2(1)

Amended and Restated Bylaws of the Registrant4.1(1)

Form of the Registrants Common Stock Certificate4.2(1)

Second Amended and Restated Investors Rights Agreement
    dated November 20, 20064.3(2)

Registration Rights Waiver and Amendment dated January 6,
    200810.1(1)

Form of Director and Executive Officer Indemnification Agreement10.2(#)

Form of Executive Officer Employment Agreement10.3#(1)

2004 Stock Plan and forms of option agreements thereunder10.4#(1)

Independent Director Compensation Policy10.5#(1)

2007 Equity Incentive Award Plan and forms of option and
    restricted stock agreements thereunder10.6(1)

Lease dated September 22, 2006 by and between the
    Registrant and Prentiss/Collins Del Mar Heights LLC10.7(1)

License Agreement dated June 27, 2003 by and between the
    Registrant and Oregon Health & Science University10.8(1)

Amendment to License Agreement dated June 27, 2003 by and
    between the Registrant and Oregon Health & Science
    University10.9(1)

Letter Agreement Amendment to License Agreement dated
    June 27, 2003 by and between the Registrant and Oregon
    Health & Science University10.10(1)

License Agreement dated March 31, 2004 by and between the
    Registrant and Duke University10.11(1)

Amendment No. 1 to License Agreement dated March 31,
    2004 by and between the Registrant and Duke University10.12(1)

Amendment No. 2 to License Agreement dated March 31,
    2004 by and between the Registrant and Duke University10.13(1)

License Agreement dated June 1, 2004 by and between the
    Registrant and Lee G. Dante, M.D.10.14(1)

License Agreement dated January 3, 2005 by and between the
    Registrant and Cypress Bioscience, Inc.10.15(1)

Credit and Security Agreement dated December 15, 2006 by
    and between the Registrant and Merrill Lynch Capital10.16(1)

Settlement Agreement dated December 14, 2006 by and among
    the Registrant, Duke University, Elan Corporation, plc, Elan
    Pharma International Ltd., Elan Pharmaceuticals, Inc., Eisai,
    Inc., Eisai Co., Ltd. and Julianne E. Jennings10.17(1)

Master Agreement for Pharmaceutical Development Services dated
    February 16, 2007 by and between Registrant and Patheon
    Pharmaceuticals Inc.10.18(3)

Consulting Agreement dated June 15, 2007 by and between the
    Registrant and PharmaDirections, Inc10.19(4)

First Amendment to Credit and Security Agreement dated
    July 2, 2007 by and between the Registrant and Merrill
    Lynch Capital1020#(5)

Amendment No. 1 to Employment Agreement dated
    August 22, 2007 by and between the Registrant and Gary D.
    Tollefson10.21(6)

Settlement Agreement dated September 12, 2007 by and among
    the Registrant, Duke University, Eisai, Inc. and Eisai Co. Ltd.10.22(7)

Second Amendment to Credit and Security Agreement dated
    November 6, 2007 by and between the Registrant and Merrill
    Lynch Capital10.23(8)

Amendment No. 3 to License Agreement dated
    December 10, 2007 by and between the Registrant and Oregon
    Health & Science University10.24(8)

Office Lease dated December 11, 2007 by and between the
    Registrant and Mullrock 3 Torrey Pines, LLC23.1

Consent of Ernst & Young LLP, independent registered
    public accounting firm 111




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##### Table of Contents



ExhibitNumber

Description31.1

Certification of Chief Executive Officer pursuant to
    Rule 13a-14
    and
    Rule 15d-14
    of the Securities Exchange Act of 1934, as amended31.2

Certification of Chief Financial Officer pursuant to
    Rule 13a-14
    and
    Rule 15d-14
    of the Securities Exchange Act of 1934, as amended32.1*

Certification of Chief Executive Officer and Chief Financial
    Officer pursuant to 18 U.S.C. 1350, as adopted pursuant to
    Section 906 of the Sarbanes-Oxley Act of 2002     (1)
    
    Filed with the Registrants Registration Statement on
    Form S-1
    on December 19, 2006, as amended (File
    No. 333-139496).(2)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on January 7, 2008.(3)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on June 20, 2007.(4)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on July 3, 2007.(5)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on August 28, 2007.(6)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on September 18, 2007.(7)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on November 8, 2007.(8)
    
    Filed with the Registrants Current Report on
    Form 8-K
    on December 14, 2007.
    
    Confidential treatment has been granted for portions of this
    exhibit. These portions have been omitted from the Registration
    Statement and filed separately with the Securities and Exchange
    Commission.#
    
    Indicates management contract or compensatory plan.*
    
    These certifications are being furnished solely to accompany
    this annual report pursuant to 18 U.S.C. Section 1350,
    and are not being filed for purposes of Section 18 of the
    Securities Exchange Act of 1934, as amended, and are not to be
    incorporated by reference into any filing of Orexigen
    Therapeutics, Inc., whether made before or after the date
    hereof, regardless of any general incorporation language in such
    filing. 112




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##### Table of Contents



SIGNATURES  Form 10-K
    By:
    /s/  Gary
    D. Tollefson   President and Chief Executive Officer
      Signature

Title

Date/s/  Gary
    D. Tollefson, M.D., Ph.D.Gary
    D. Tollefson, M.D., Ph.D.

President, Chief Executive Officer and Director (Principal
    Executive Officer)

March 27, 2008/s/  Graham
    K. CooperGraham
    K. Cooper

Chief Financial Officer and Treasurer (Principal Financial and
    Accounting Officer)

March 27, 2008/s/  Eckard
    Weber, M.D.Eckard
    Weber, M.D.

Chairman of the Board of Directors

March 27, 2008/s/  Louis
    C. BockLouis
    C. Bock

Director

March 27, 2008/s/  Brian
    H. DoveyBrian
    H. Dovey

Director

March 27, 2008/s/  Joseph
    S. LacobJoseph
    S. Lacob

Director

March 27, 2008/s/  Michael
    F. Powell, Ph.D.Michael
    F. Powell, Ph.D.

Director

March 27, 2008/s/  Daniel
    K. Turner IIIDaniel
    K. Turner III

Director

March 27, 2008  113