Exhibit 10.27

CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION

EXECUTION VERSION

AMENDED AND RESTATED LICENSE AGREEMENT

THIS AMENDED
AND RESTATED LICENSE AGREEMENT (this Agreement) is entered into as of the 6thday of December, 2010 (the A&R Effective Date) by and between GlaxoSmithKline LLC (formerly known as SmithKline Beecham Corporation, doing business as GlaxoSmithKline), a Delaware
limited liability company located at One Franklin Plaza, Philadelphia, PA 19102 (GSK LLC), Glaxo Group Limited, a private limited company incorporated in England and Wales, having its registered office at Glaxo Wellcome House,
Berkeley Avenue, Greenford, Middlesex, England UB6 0NN (GGL, and together with GSK LLC, GSK) and Orexigen Therapeutics, Inc., a Delaware corporation located at 3344 N. Torrey Pines Court, Suite 200, La Jolla,
California 92037 (Orexigen). GSK and Orexigen are sometimes collectively referred to herein as the Parties and separately as a Party.

WHEREAS, GSK and Orexigen are parties to that certain License Agreement dated as of June 10, 2009 (the
Original License Agreement), pursuant to which GSK granted to Orexigen a non-exclusive license under the Licensed Patents to develop and commercialize Licensed Product in the Field in the Territory (as each such term is
hereinafter defined);

WHEREAS, [* * *]; and

WHEREAS, Orexigen and GSK desire to amend and restate in its entirety the Original License Agreement as set forth in this Agreement below.

NOW, THEREFORE, in consideration of the mutual covenants and agreements set forth herein and other good and valuable consideration, the
receipt and legal sufficiency of which are hereby mutually acknowledged, the Original License Agreement is hereby amended and restated, effective as of the A&R Effective Date, as follows:

Article 1. Definitions.

Section 1.1 As used herein, the following
capitalized terms will have the meanings set forth below when used in this Agreement, and all terms defined in the singular will have the same meanings when used in the plural (and vice versa), unless otherwise specified.

AAA will have the meaning set forth in Section 10.1.

Affiliate(s) of a Party or Person means any Person(s), whether directly or indirectly, Controlling, Controlled by, or
under common Control with, such Party or Person, as applicable.

Agreement will have the meaning set forth
in the Preamble.

Applicable Law means all provisions of any and all federal, national, state, provincial
or local statutes, laws, rules, regulations, administrative codes, ordinances, decrees, orders,



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decisions, injunctions, awards judgments, permits and licenses of or from governmental authorities in the
Territory that apply to the use or regulation of the Licensed Product.

Business Day means any day other
than a day that is a Saturday, a Sunday or a federal holiday in the United States.

Canadian Patents means
[* * *]

Change of Control means the occurrence of any of the following events:

(a) a merger or consolidation of Orexigen with or into any other corporation or other entity or person;

(b) a sale, exchange or other transfer in one transaction or a series of related transactions of all or substantially all of
Orexigens assets;

(c) a liquidation or dissolution of Orexigen; or

(d) a sale or transfer of Orexigens voting securities in one transaction or a series of related transactions that will result in
the transfer of ownership of fifty percent (50%) or more of the voting securities of Orexigen or in one Person or an affiliated group of Persons owning fifty percent (50%) or more of the voting securities of Orexigen;

provided, that the following events shall not constitute a Change of Control: (i) a merger, sale, transfer or consolidation of Orexigen
in which the holders of the voting securities of Orexigen immediately prior to the merger, sale, transfer or consolidation hold at least a majority of the voting securities in the successor corporation immediately after the merger or consolidation;
(ii) a sale, lease, exchange or other transaction in one transaction or a series of related transactions of all or substantially all of Orexigens assets to a wholly owned subsidiary corporation; (iii) a mere reincorporation of
Orexigen; or (iv) a transaction undertaken for the sole purpose of creating a holding company that will be owned in substantially the same proportion by the persons who held Orexigens securities immediately before such transaction;
provided further, that in the cases of clauses (ii), (iii) and (iv), such subsidiary, reincorporated entity or holding company shall sign a joinder to this Agreement agreeing to be jointly and severally responsible for all of Orexigens
obligations and liabilities hereunder.

Claim has the meaning set forth in Section 10.2.

Confidential Information means any and all information disclosed to or obtained by the Parties pursuant to or in
connection with the negotiation, execution, delivery and performance of this Agreement or the consummation of the transactions contemplated hereby and any and all information regarding, related to, or associated with any or all elements of this
Agreement including the Licensed Patents; provided, however, that Confidential Information will not include information that: (i) at the time of disclosure is in the public domain; (ii) after disclosure becomes part of the public domain,
except through breach of this Agreement; (iii) a Party can demonstrate by reasonable proof was in its possession prior to the time of disclosure by the other Party hereunder, and was not acquired directly or indirectly from the other Party;
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demonstrate by reasonable proof was developed by or on behalf of such Party independent of and without reference to the other Partys Confidential Information; or (v) becomes available
to a Party from a Third Party who did not acquire such information directly or indirectly from the other Party and who is not otherwise prohibited from disclosing such information.

Control means (i) direct or indirect ownership of more than fifty percent (50%) of the equity (or such
lesser percentage that is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction) having the power to vote on or direct the affairs of such Party or Person, as applicable, or (ii) the power to direct decisions of
such Party or Person, as applicable, including, without limitation, the power to direct management and policies of such Party or Person, as applicable, whether by reason of ownership, by contract or otherwise (and the expressions
Controlling and Controlled shall be construed accordingly).

Disclosing
Party will have the meaning set forth in Section 5.1.

Dispute will have the meaning set
forth in Section 10.1.

Dispute Notice will have the meaning set forth in Section 10.1.

Effective Date means June 10, 2009.

FDA means the United States Food and Drug Administration.

Field means the treatment of obesity and disorders of weight management [* * *]

Further Sublicensee will have the meaning set forth in Section 2.2.

GSK will have the meaning set forth in the Preamble.

GSK Indemnitees will have the meaning set forth in Section 10.2.

Indemnitee will have the meaning set forth in Section 10.4.

Indemnitor will have the meaning set forth in Section 10.4.

Knowledge of GSK means the [* * *].

Licensed Patents means (a) [* * *]; (ii) any foreign equivalents of the [* * *]; (iii) any patents claiming priority from or common priority with the [* * *]; and
(iv) all divisions, continuations, continuations-in-part, provisionals, reissues, reexaminations, substitutions or extensions of the [* * *], whether foreign or domestic, and any patents that issue thereon, and any reissues, reexaminations
renewals or extensions (including any supplemental protections certificate) of any such patent, including all foreign counterparts of any of the foregoing; provided, however, that for clarity, nothing contained in subpart (b) of this definition
shall be deemed to include, or be a reference to, the [* * *] or any other [* * *].



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Licensed Product means any prescription
pharmaceutical product comprising a formulation of bupropion hydrochloride and naltrexone that is intended for twice daily or more frequent dosage (other than for dose escalation as indicated in the label) and that is intended to be marketed with
the trade name Contrave®, provided, however, that [* * *]

Losses will have the meaning set forth in Section 10.2.

Major Market means any of the United Kingdom, Germany, France, Italy and Spain.

New Drug Application means a New Drug Application filed with the FDA including a 505(b)(2) application.

Orexigen will have the meaning set forth in the Preamble.

Orexigen Indemnitees will have the meaning set forth in Section 10.3.

Product Partnering Agreement means an agreement for the co-promotion, co-marketing, partnership, license, sale
or other similar arrangement for Licensed Product.

Party or Parties will have
the meaning set forth in the Preamble.

Person means any individual, corporation, partnership, firm,
association, joint venture, joint stock company, trust or other entity, or any government or regulatory administrative or political subdivision or agency, department or instrumentality thereof.

Receiving Party will have the meaning set forth in Section 5.1.

Regulatory Approval means marketing approval from the FDA or from agencies in foreign jurisdictions that provide
approval for marketing or distributing drugs in those jurisdictions.

Royalty(ies) will have the meaning
set forth in Section 3.1.

Sublicense means a sublicense agreement with any Sublicensee or any Further
Sublicensee.

Sublicensee will have the meaning set forth in Section 2.2.

Term will have the meaning set forth in Section 8.1.

Territory means all countries and territories in the world.

Third Party means any Person other than the Parties.

Trade Dress means any and all designs, colors, graphics and Trademarks of Licensed Product packaging, these elements
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Trademark means any and all trademarks, service marks, words, phrases,
slogans, designs, logos and combinations thereof used as an indication of source of Licensed Product or associated services or products.

United States or U.S. means the fifty (50) states of the United States of America, its territories and the District of Columbia.

Section 1.2 The word including or any variation thereof means including without limitation and will not be
construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.

Article
2. Patent License Grant; Covenant Not to Sue.

Section 2.1 Non-Exclusive Patent License Grant.

(i) Subject to the terms and conditions of this Agreement, including, without limitation, Section 11.3(vi), GSK, on
behalf of itself and its Affiliates, hereby grants to Orexigen a non-exclusive license, with the right to grant sublicenses solely for the purposes as set forth in Section 2.2, under the Licensed Patents, to make, have made, use, sell, offer
for sale and import and to file for and obtain Regulatory Approval for Licensed Product in the Field in the Territory.

(ii) Without prejudice to the provisions of Section 2.5, Orexigen expressly acknowledges and agrees that except as set forth in Section 2.1(i), neither GSK nor any of its Affiliates is in any
way granting to Orexigen or any of its Affiliates, Sublicensees or Further Sublicensees any rights under any patents or patent applications other than the Licensed Patents that are or may become owned by GSK or any of its Affiliates, or to which GSK
or any of its Affiliates otherwise has, now or in the future the right to grant licenses and license rights or sublicenses and sublicense rights. Further, Orexigen expressly acknowledges and agrees that (a) the non-exclusive license under the
Licensed Patents granted by GSK to Orexigen as provided in Section 2.1(i) is solely with respect to the making, having made, using, selling, offering for sale and importing of and filing for and obtaining Regulatory Approval of Licensed Product
in the Field in the Territory; and (b) the non-exclusive license under the Licensed Patents granted by GSK to Orexigen as provided in Section 2.1(i) is in no way deemed directly or impliedly to be a license under, and Orexigen disclaims
all direct or implied rights under, the Licensed Patents or any other patents that, in each case, are or may become owned by GSK or any of its Affiliates, or to which GSK or any of its Affiliates otherwise has, now or in the future, that are related
to, regarding or associated in any way with the making, having made, using, selling, offering for sale or importing of any pharmaceutical product or formulation within and without the Field and within and without the Territory, other than the
Licensed Product.

Section 2.2 Sublicense of Rights. Subject to the terms and conditions of this Agreement, and
notwithstanding anything to the contrary in Section 11.3(vi), the Parties agree that Orexigen may [* * *] sublicense any or all of its rights under this Agreement (including but not limited to those set forth in Section 2.1) to a Third
Party solely (i) in connection with Regulatory Approval for the Licensed Product for Orexigen (without the right to further sublicense) or (ii) in connection with a Product Partnering Agreement (any such party, a



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Sublicensee). Notwithstanding anything to the contrary in this Section 2.2 or Section 11.3(vi), the Parties agree that a Sublicensee pursuant to Section 2.2(ii),
including Orexigens Sublicensee, Takeda Pharmaceutical Company Limited, may [* * *] sublicense any or all of its rights under this Agreement to an Affiliate or another Third Party (any such party, a Further Sublicensee).
Orexigen acknowledges and agrees that in no event will a Sublicense to any Sublicensee or any Further Sublicensee of any or all rights under this Agreement be deemed to relieve Orexigen of its liabilities or obligations to GSK under this Agreement.
Orexigen expressly acknowledges and agrees that it will remain fully and unconditionally obligated and responsible for the full and complete performance of all of its obligations under the terms and conditions of this Agreement. In the event that
Orexigen elects to sublicense as provided in this Section 2.2(ii), it will provide GSK with written notice thereof, which notice will include the identity and address of any Sublicensee, prior to the execution of any such Sublicense by
Orexigen. Orexigen represents and warrants that the terms of any Sublicense will refer to this Agreement and Orexigen shall ensure that none of the terms of any Sublicense shall conflict with the terms of this Agreement. In the event of a conflict
between the terms of this Agreement and the terms of any Sublicense, as between Orexigen and GSK, and/or as to any rights and/or obligations under this Agreement that are sublicensed to any Sublicensee or Further Sublicensee as provided herein, the
terms of this Agreement will prevail.

Section 2.3 Affiliates. Either Party may contract or agree with one or more of
its Affiliates to have such Affiliate perform any of such Partys obligations herein. In no event will such use of an Affiliate be deemed to relieve a Party of its liabilities or obligations to the other Party under this Agreement. Each Party
expressly acknowledges and agrees that it will remain fully and unconditionally obligated and responsible for the full and complete performance of all of its obligations under the terms and conditions of this Agreement, whether or not such
performance is carried out by such Party or any of its Affiliates.

Section 2.4 Covenant Not to Sue of Orexigen. During
the term of this Agreement (and as further provided in Section 8.4), Orexigen covenants that neither it nor any of its Sublicensees or Further Sublicensees or their respective Affiliates will initiate or bring, nor will it nor any of its
Sublicensees or Further Sublicensees or their respective Affiliates assist in any way any Person in pursuing, a lawsuit, proceeding, interference or any other action of any kind whatsoever that either (i) seeks a judicial determination that the
Licensed Product does not infringe on any of the Licensed Patents, or (ii) challenges the validity, enforceability or scope of any of the Licensed Patents, provided, that this Section 2.4 shall not apply in the event that GSK or any of its
Affiliates breaches the covenant not to sue in Section 2.5.

Section 2.5 Covenant Not to Sue of GSK. During the
term of this Agreement, GSK covenants that neither it nor any of its Affiliates will, under the Licensed Patents, initiate or bring a lawsuit, proceeding or other action of any kind whatsoever that claims that the making, having made, using,
selling, offering for sale or importing, or seeking, obtaining or maintaining Regulatory Approval of, Licensed Product in the Field in the Territory by Orexigen, any of its Affiliates or any permitted Sublicensee or Further Sublicensee is infringing
the Licensed Patents, provided, that this Section 2.5 shall not apply in the event that Orexigen or any of its Sublicensees or Further Sublicensees or their respective Affiliates breaches the covenant not to sue in Section 2.4.



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Article 3. Royalty Payments to GSK.

Section 3.1 Royalties. The Parties acknowledge that, in consideration for the rights and licenses granted to Orexigen by GSK
pursuant to Article 2, Orexigen has paid in full the following royalty payments (the Royalties) to GSK:



|                              |  |                                             
|----------------------------- |  | --------------------------------------------
|Milestones                    |  | Royalty                                     
|(1) Effective Date            |  | U.S. $[* * *]                               
|                              | 
|(2) The earliest to occur of: |  | U.S. $[* * *] (the Second Royalty Payment)
|                              | 
|(a) [* * *];                  |  |                                             
|                              | 
|(b) [* * *];                  |  |                                             
|                              | 
|(c) [* * *]; or               |  |                                             
|                              | 
|(d) [* * *]                   |  |                                             

Section 3.2 Royalty Payment Provisions.

(i) All Royalties are non-refundable.

(ii) All Royalties shall be paid by Orexigen, in U.S. Dollars, by wire transfer of immediately available funds to
GSKs account listed on Exhibit A, or to such other account as GSK designates in writing to Orexigen. Orexigen shall send written confirmation of such payments of Royalties at the time they are made to the addresses set forth in
Section 11.1.

(iii) In no event shall Orexigen have any right to reclaim any Royalties already paid to
GSK.

(iv) The Royalties shall be internally allocated by GSK as follows: [* * *]% to SB and [* * *]% to GGL.

Article 4. Product Development and Commercialization. As of the Effective Date and during the Term, Orexigen will have full
control, authority and responsibility over research, development, registration, manufacture, commercialization, marketing and sale of all Licensed Product in each country in the Field in the Territory, and all such activity will be undertaken at
Orexigens or its Sublicensees or Further Sublicenseess sole expense and discretion.



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Article 5. Confidential Information.

Section 5.1 Confidential Information. During the Term, and for a period of five (5) years after the effective date of the
expiration or earlier termination of this Agreement for any permitted reason contained herein, the Parties agree that:

(i) The Parties will not disclose, directly or indirectly, in any manner whatsoever to any Third Parties any Confidential Information received from the other Party (the Disclosing
Party) without first obtaining the written consent of the Disclosing Party which such consent shall not be unreasonably withheld, conditioned or delayed, and the Parties will keep confidential, all of the Disclosing Partys
Confidential Information that is disclosed to such Party (the Receiving Party), provided that a Party may disclose the specific terms of this Agreement (a) to attorneys, accountants, advisors, lenders, investors and bona fide
prospective lenders and investors who are bound by obligations of confidentiality no less restrictive than those set forth herein or who are otherwise bound by ethical or other similar obligations, or (b) pursuant to business discussions
wherein a letter of intent or binding agreement has been executed or a term sheet has been completed relating to a sale of substantially all the assets of Orexigen, an equity investment in Orexigen, a merger, a sublicense permitted hereunder, or a
Change of Control, so long as such discussions are subject to a nondisclosure agreement. The Receiving Party agrees to use the same level of care in safeguarding the Disclosing Partys Confidential Information that the Receiving Party uses with
its own confidential information of a similar nature, but in no event less than reasonable care. The Receiving Party will restrict disclosure of the Disclosing Partys Confidential Information solely to those of its (or its Affiliates or
any Sublicensees or Further Sublicensees) employees or representatives having a need to know such Confidential Information in order to accomplish the purposes of this Agreement. The Receiving Party represents that its employees and
representatives who will have access to the Disclosing Partys Confidential Information are bound by an obligation to maintain such Confidential Information in accordance with the confidentiality obligations set forth in this Article 5.

(ii) The Receiving Party will not use the Disclosing Partys Confidential Information in any manner
whatsoever other than solely in connection with the performance of its obligations under this Agreement or as otherwise expressly permitted by the Disclosing Party in writing.

(iii) Except as set forth herein in Section 5.1(i), the Receiving Party will not, directly or indirectly, without the
Disclosing Partys prior written consent, disclose in any manner whatsoever to any Third Party the fact that the Disclosing Partys Confidential Information exists or has been made available to the Receiving Party, or disclose in any
manner whatsoever to any Third Party any provisions, or terms, or conditions, or any other fact relating to this Agreement, that this Agreement exists.

(iv) In the event that the Receiving Party is required by Applicable Law in the Territory, or requested by a governmental body or regulatory agency in the Territory, to disclose any of the Disclosing
Partys Confidential Information, the Receiving Party will notify the Disclosing Party promptly so that the Disclosing Party may seek a protective order or other appropriate remedy or, in the Disclosing Partys sole discretion, waive
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confidentiality provisions of this Agreement. At the Disclosing Partys expense, the Receiving Party will co-operate in all reasonable respects, in connection with any reasonable actions to
be taken for the foregoing purpose. In the event that no such protective order or other remedy is obtained, or that the Disclosing Party waives compliance with the confidentiality provisions of this Agreement, the Receiving Party will, without
liability hereunder, furnish only that portion of the Confidential Information to such governmental body or agency that the Receiving Party is advised by its counsel is required to be disclosed by Applicable Law, and the Receiving Party will
exercise reasonable efforts to obtain reliable assurances that confidential treatment will be accorded the Disclosing Partys Confidential Information.

(v) Upon the effective date of the termination of this Agreement for any reason, the Disclosing Party may so request in writing, and the Receiving Party will either: (a) promptly destroy all copies
of the Disclosing Partys Confidential Information in the possession of the Receiving Party and confirm such destruction in writing to the Disclosing Party; or (b) promptly deliver to the Disclosing Party, at the Receiving Partys
expense, all copies of such Confidential Information in the possession of the Receiving Party. Additionally, upon termination of this Agreement for any reason, the Receiving Party will immediately cease all use of the Disclosing Partys
Confidential Information including, without limitation, removing all references to such Confidential Information from its internal analyses, memoranda, compilations, studies or other documents. All Confidential Information will continue to be
subject to the terms of this Agreement for the period set forth in this Section 5.1.

(vi) The Disclosing
Party may seek to enforce all rights and legal remedies available under this Article 5 or by law, including, without limitation, injunctive relief, specific performance and other equitable remedies in the event of a breach of the provisions of this
Article 5 by the Receiving Party, and the Receiving Party will not object to such attempt at enforcement on the grounds that there is adequate remedy at law.

Section 5.2 Publicity. Other than as required by the Applicable Law in the Territory, no public announcement or other disclosure to any Third Party in any manner whatsoever concerning the specific
terms will be made, either directly or indirectly, by either Party, without first obtaining the prior written consent of the other Party, which such consent may not be unreasonably withheld conditioned or delayed, provided that a Party may disclose
the specific terms of this Agreement (a) to attorneys, accountants, advisors, lenders, investors and bona fide prospective lenders and investors who are bound by obligations of confidentiality no less restrictive than those set forth herein or
who are otherwise bound by ethical or other similar obligations, or (b) pursuant to business discussions wherein a letter of intent or binding agreement has been executed or a term sheet has been completed relating to a sale of substantially
all the assets of Orexigen, an equity investment in Orexigen, a merger, a sublicense permitted hereunder, or a Change of Control, so long as such discussions are subject to a nondisclosure agreement. In addition, in the event that either Party is
requested by a governmental body or regulatory agency to disclose the terms or subject matter of this Agreement, such Party will notify the other Party promptly so that such other Party may seek a protective order or other appropriate remedy or, in
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compliance with the terms of this Section 5.2. In the event that no such protective order or other remedy is obtained, or that such other Party waives compliance with the confidentiality
provisions of this Agreement, the Party that has been requested to make a disclosure will, without liability hereunder, furnish only that portion of the information relating to the terms or subject matter of this Agreement to such governmental body
or agency that such Party is advised by its counsel is required to be disclosed by Applicable Law, and such Party will exercise reasonable efforts to obtain reliable assurances that confidential treatment will be accorded the information being
disclosed.

Article 6. Patent Prosecution and Litigation.

Section 6.1 Responsibility for Licensed Patents. GSK (and its Affiliates) will at all times, during the Term and after the
expiration or earlier termination thereof for any reason, solely own all right, title and interest in and to the Licensed Patents [* * *]. During the Term, GSK will continue to have responsibility for and control over, at its sole cost and expense,
the prosecution and maintenance of the Licensed Patents, with the exception of the Canadian Patents. GSK shall use commercially reasonable efforts to maintain the Licensed Patents, [* * *].

Section 6.2 Patent Infringement. In the event that either Party becomes aware of actual or threatened infringement of a patent
included within Licensed Patents in the Territory, that Party will promptly notify the other Party in writing. In respect of the Licensed Patents, with the exception of the Canadian Patents, GSK will have the sole right, but not the obligation, to
bring, at its own expense, an infringement action against any Third Party and GSK will have full control over its conduct, including settlement thereof. If GSK, at its sole discretion, elects to bring an infringement action against any Third Party,
GSK shall use commercially reasonable efforts to enforce the Licensed Patents, [* * *].

Section 6.3 Infringement by Third
Parties. Each Party shall promptly report to the other Party any infringement or any unauthorized use or misuse of the Licensed Patents that may come to its attention. The Parties acknowledge that GSK shall have the right to promptly report [* *
*] any infringement or any unauthorized use or misuse [* * *] that may come to the attention of either of the Parties, provided that [* * *] shall be under obligations of confidentiality and non-use, that are no less restrictive than those set forth
in Article 5, with respect to any Confidential Information of Orexigen so reported to [* * *] (provided that, subject to the licenses and sublicenses granted herein with respect to the Licensed Patents [* * *]).

Article 7. Trademarks. Orexigen will be responsible for the selection of all Trademarks, Trade Dress, copyrights, packaging, selling marks
(e.g., taglines and slogan marks), and advertising that it employs in connection with Licensed Product in the Field in the Territory and will own and control such Trademarks, Trade Dress, copyrights, packaging, selling marks (e.g., taglines and
slogan marks), and advertising Orexigen uses with regard to the Licensed Product in the Field in the Territory.



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Article 8. Term and Termination.

Section 8.1 Term. The term of this Agreement (the Term) will commence on the Effective Date and, unless sooner
terminated as provided in Section 8.2 or Section 8.3, will expire, on a country-by-country basis, on the date of the expiration, lapse or invalidation (by a decision of a court or regulatory authority in such country that is non-appealable
or not appealed within the time allowed for appeal) of the last remaining patent or patent application within the Licensed Patents in such country. Upon the expiration of this Agreement in any country of the Territory under this provision, Orexigen
will be permitted to make, have made, use, sell, offer for sale and import and file for and obtain Regulatory Approval of Licensed Product in the Field in such country on a fully paid-up, royalty-free basis without further obligation to GSK.

Section 8.2 Termination by Orexigen. Orexigen may immediately terminate this Agreement with respect to any country in
the Territory or in its entirety at any time during the Term, for any reason whatsoever, by giving GSK [* * *] ([* * *]) Business Days prior written notice thereof; provided, however, that before the milestone occurs that triggers the Second
Royalty Payment obligation, Orexigen may only exercise such right to terminate the Agreement with respect to any country in the Territory or in its entirety with such written notice if Orexigen determines in good faith, using the same standards that
Orexigen would use in assessing whether or not to continue the development or commercialization of a product of its own making, that the patent, medical/scientific, technical, regulatory or commercial profile of Licensed Product does not justify the
continued development and/or commercialization of Licensed Product in such country.

Section 8.3 Termination by the
Parties.

(i) The Parties may terminate this Agreement at any time and for any reason during the Term upon
their mutual written agreement.

(ii) Termination for Breach

(a) Each Party will be entitled to terminate this Agreement by giving written notice to the other Party in the event that
the other Party is in material default or breach of any of its obligations hereunder and fails to remedy any such default or breach within [* * *] ([* * *]) days after notice thereof by the non-defaulting/non-breaching Party (provided that such cure
period shall be [* * *] ([* * *]) days with respect to any breach of Orexigens payment obligations hereunder). If such default or breach is not corrected within the foregoing cure period, the non-defaulting/non-breaching Party will have the
right to immediately terminate this Agreement by giving written notice to the Party in default or breach, provided the notice of termination is given within [* * *] ([* * *]) months of the default and prior to correction of the default or breach. In
the event of a termination by GSK pursuant to this Section 8.3(ii)(a), this Agreement and all licenses granted hereunder shall be deemed terminated as of the effective date of such termination notice.

(b) Orexigen has furnished written notice to GSK of the identity and address of its Sublicensee, Takeda Pharmaceutical
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shall provide contemporaneous written notice to such Sublicensee (at the address set forth in the notice provided pursuant to Section 2.2) of any notice of material default or breach of any
provision of this Agreement being furnished to Orexigen as provided in Section 8.3(ii)(a).

(iii) Either
Party may terminate this Agreement in its entirety at any time during the Term by giving written notice to the other Party: (A) if such other Party files in any court or agency, pursuant to any statute or regulation of any state or country, a
petition in bankruptcy or insolvency or for the reorganization or for an arrangement or for the appointment of a receiver or trustee of such other Party or of its assets; or (B) if such other Party is served with an involuntary petition against
it, filed in any insolvency proceeding, and such petition will not be dismissed with [* * *] ([* * *]) days after the filing thereof; or (C) if such other Party proposes or is a party to any dissolution or liquidation; or (D) if such other
Party makes an assignment for the benefit of creditors.

Section 8.4 Rights and Duties upon Expiration or Termination.

(i) Termination or expiration of this Agreement for any reason will terminate all outstanding obligations and
liabilities between the Parties arising from this Agreement except those described in:

(a) Section 8.1;

(b) This Section 8.4;

(c) Article 10;

(d) Article 11; and

(e) Article 1 for the sole purposes of
interpreting the obligations and liabilities between the Parties surviving termination of this Agreement;

which obligations and liabilities
will survive termination or expiration of this Agreement indefinitely.

(ii) Notwithstanding the foregoing, in
the event that GSK terminates this Agreement pursuant to Section 8.3(ii) due to the failure of Orexigen to make any payment owed to GSK under Section 3.1 of this Agreement, Section 2.4 shall survive such termination

(iii) Upon termination of this Agreement, GSK will have the right to retain any sums already paid by Orexigen hereunder.

(iv) Termination of this Agreement in accordance with the provisions hereof will not limit remedies that may
be otherwise available in law or equity.

(v) For the avoidance of doubt, upon the termination of this
Agreement by GSK pursuant to Section 8.3, GSKs grant of a license under the Licensed Patents to Orexigen



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pursuant to Article 2 hereof, will terminate and Orexigen will no longer have rights under the Licensed Patents.

Article 9. Representations, Warranties and Covenants.

Section 9.1
GSK and Orexigen each hereby represent and warrant to the other as follows:

(i) It is a corporation,
respectively, duly organized, validly existing and is in good standing under the laws of its jurisdiction of formation, and has all requisite power and authority, corporate or otherwise, to execute, deliver and perform this Agreement.

(ii) The execution, delivery and performance of this Agreement have been duly authorized by all necessary corporate action
and do not and will not (a) require any consent or approval of its stockholders, (b) violate any provision of any Applicable Law or any provision of its certificate of incorporation, by-laws or other founding document, or (c) result
in a breach of or constitute a default under any material agreement, mortgage, lease, license, permit or other instrument or obligation to which it is a party or by which it or its properties may be bound or affected.

(iii) It is not under any obligation to any Person, contractual or otherwise, that is conflicting or inconsistent in any
respect with the terms of this Agreement or that would impede the diligent and complete fulfillment of its obligations hereunder.

(iv) This Agreement is a legal, valid and binding obligation enforceable against it in accordance with its terms and conditions, except as such enforceability may be limited by applicable bankruptcy,
insolvency, moratorium, reorganization or similar laws, from time to time in effect, affecting creditors rights generally.

Section 9.2 GSK represents and warrants to Orexigen that:

(i) GSK
and its Affiliates hold all right, title and interest in and to the Licensed Patents [* * *], and neither GSK nor its Affiliates have granted, transferred or assigned [* * *] nor will grant, transfer or assign any rights to the Licensed Patents that
are inconsistent with or that limit the rights granted to Orexigen under this Agreement;

(ii) [* * *];

(iii) [* * *];

(iv) GSK has the full and unconditional right and ability to grant the licenses specified in Section 2.1 and Section 2.2 of this Agreement and to grant the covenant not to sue under
Section 2.5;

(v) With regard to the Canadian Patents, (a) there are (1) no other Canadian
patents claiming priority from or common priority with the Canadian Patents; and (2) no divisionals, continuations, continuations-in-part, provisionals, reissues, reexaminations,



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substitutions or extensions of the Canadian Patents, pending or in force, as the case may be, in Canada; and (b) [* * *] claiming or disclosing any Licensed Products [* * *].

(vi) [* * *]; and

(vii) The Licensed Patents [* * *] are free and clear of any liens, mortgages, security interests, charges and encumbrances as of the Effective Date. [* * *] are free and clear of any liens, mortgages,
security interests, charges and encumbrances as of the Effective Date [* * *].

Section 9.3 Orexigen represents and
warrants to GSK that Orexigen has the full and unconditional right and ability to grant the covenant not to sue under Section 2.4.

Section 9.4 EXCEPT FOR THE EXPRESS WARRANTIES AND REPRESENTATIONS AND COVENANTS CONTAINED IN THIS AGREEMENT, NEITHER LICENSOR NOR LICENSEE MAKES, AND EACH HEREBY EXPRESSLY DISCLAIMS, ANY WARRANTIES OR
REPRESENTATIONS, EITHER EXPRESS OR IMPLIED, WHETHER IN FACT OR IN LAW, INCLUDING WITHOUT LIMITATION IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR ANY WARRANTIES OR REPRESENTATIONS AS TO VALIDITY OR ENFORCEABILITY OF
THE LICENSED PATENTS.

Article 10. Dispute Resolution and Indemnification.

Section 10.1 Dispute Resolution. If a dispute or controversy regarding any right or obligation under this Agreement arises between
the Parties that they are unable to resolve (a Dispute), each of the Parties will, within a reasonable amount of time after any such Dispute arises but in no event not more than [* * *] ([* * *]) Business Days after such Dispute
arises (or in the event that there is a cure period as provided in Section 8.3(ii), within [* * *] ([* * *]) Business Days after the expiration of the applicable cure period), be entitled to submit to the other Party written notice of such
Dispute, with such notice setting forth in reasonable detail the nature of the dispute (the Dispute Notice). For a period of [* * *] ([* * *]) Business Days after the date of the receiving Partys receipt of the Dispute
Notice, the Parties will seek to resolve such Dispute by good faith negotiation between representatives of the Parties. If at the end of such [* * *] ([* * *]) day period the Dispute remains unresolved, such Dispute will be presented to [* * *] or
his designee and the Chief Executive Officer of Orexigen or his designee, for resolution of such Dispute by good faith negotiations. If at the end of a subsequent [* * *] ([* **]) Business Day period the Dispute remains unresolved, the Parties
may only seek relief for such Dispute by referring such Dispute to arbitration under the rules of American Arbitration Association (the AAA), subject to Section 11.2. The arbitration will be conducted by a panel of three
(3) arbitrators, one of which shall be selected by GSK, one of which shall be selected by Orexigen, and one of which shall be jointly selected by the first two arbitrators (or, in the absence of their agreement within [* * *] ([* * *]) days, by
the AAA), in the City of New York, NY. The costs of the three arbitrators and the AAA shall be [* * *]. The decision of such arbitration panel will be final and binding upon the Parties, and judgment upon such award may



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be entered in any court having jurisdiction thereof. The provisions of this Section 10.1 will not restrict in any way the Parties rights to seek preliminary injunctive or other
equitable relief from any court having jurisdiction.

Section 10.2 Orexigen Indemnification Obligations. Orexigen will
indemnify, defend and hold harmless GSK, its Affiliates, and their respective officers, directors, trustees, agents and employees (collectively, GSK Indemnitees), from and against any and all losses, liabilities, claims,
obligations, demands, awards, settlements, penalties, suits, damages, costs, fees and expenses, including, except to the extent provided otherwise in Section 10.4, reasonable attorneys fees and expenses (collectively,
Losses), directly arising from any action, suit, demand, complaint or other form of proceeding (a Claim) made or brought against a GSK Indemnitee by or on behalf of a Third Party, solely to the extent that such
Claim is based on or arises out of or in connection with:

(i) The negligent, grossly negligent, reckless or
willful actions or omissions of any Orexigen Indemnitee or any Sublicensee or any Further Sublicensee, or their respective officers, trustees, agents and employees, in performing Orexigens obligations under this Agreement or a
Sublicensees or a Further Sublicensees obligations under a Sublicense;

(ii) the material breach of
any covenant, warranty or representation, whether express or implied, made by Orexigen under this Agreement or by a Sublicensee or a Further Sublicensee under a Sublicense;

(iii) the death of, injury to, or damage to property of any Person resulting from the production, manufacture, sale, use,
lease, consumption or advertisement of Licensed Product; and/or

(iv) any material violation of Applicable Law
by any Orexigen Indemnitee, a Sublicensee or a Further Sublicensee, or any of their respective Affiliates or officers, directors, trustees, agents or employees.

Provided, however, Orexigen will not indemnify and hold any GSK Indemnitees harmless for the items set forth in items (i) through (iv) of this Section 10.2 to the extent such item was
attributable to the legal fault of any GSK Indemnitee, or the negligent, grossly negligent or intentional wrongful acts or omissions of any GSK Indemnitee, or any GSK Indemnitees failure to comply in any material respect with the provisions of
this Agreement, or any GSK Indemnitees failure to comply in any material respect with Applicable Law, or any matter for which GSK is obligated to indemnify a Orexigen Indemnitee as provided in Section 10.3.

Section 10.3 GSK Indemnification Obligations. GSK will indemnify, defend and hold harmless Orexigen, its Affiliates, and their
respective officers, directors, trustees, agents and employees (collectively, Orexigen Indemnitees), from and against any and all Losses directly arising from any Claim made or brought against an Orexigen Indemnitee by or on
behalf of a Third Party, solely to the extent that such Claim is based on or arises out of:



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(i) the material breach of any covenant, warranty or representation, whether
express or implied, made by GSK under this Agreement [* * *]; and/or

(ii) any material violation of Applicable
Law by any GSK Indemnitee, or any of their respective Affiliates.

Provided, however, GSK will not indemnify and hold Orexigen Indemnitees
harmless for the items set forth in items (i) and (ii) of this Section 10.3 to the extent such item was attributable to the legal fault of any Orexigen Indemnitee, or the negligent, grossly negligent or intentional wrongful acts or
omissions of any Orexigen Indemnitee, or any Orexigen Indemnitees failure to comply in any material respect with the provisions of this Agreement, or any Orexigen Indemnitees failure to comply in any material respect with Applicable Law,
or any matter for which Orexigen is obligated to indemnify a GSK Indemnitee as provided in Section 10.2.

Section 10.4
Indemnity Procedures. A Person entitled to indemnification pursuant to either Section 10.2 or Section 10.3 will hereinafter be referred to as an Indemnitee. A Party obligated to indemnify an Indemnitee hereunder
will hereinafter be referred to as an Indemnitor. In the event an Indemnitee is seeking indemnification under either Section 10.2 or Section 10.3, the Indemnitee will inform the Indemnitor of a Claim as soon as
reasonably practicable after it receives notice of the Claim; provided that the failure so to notify the Indemnitor shall not relieve it of any liability that it may have to any Indemnitee hereunder, except to the extent the Indemnitor demonstrates
that it is materially prejudiced thereby. The Indemnitee will permit the Indemnitor to assume direction and control of the defense of the claim (including the right to settle the Claim solely for monetary consideration), and, at the
Indemnitors expense, will cooperate as reasonably requested in the defense of the Claim. The Indemnitee will have the right to retain its own counsel at its own expense. The Indemnitor may not settle such Claim, or otherwise consent to an
adverse judgment in such Claim, that would subject the Indemnitee to an injunction or if such settlement or judgment would materially diminish or limit or otherwise adversely affect the rights, activities or financial interests of the Indemnitee,
without the express written consent of the Indemnitee, which consent shall not be unreasonably withheld or delayed so long as (i) there is no finding or admission of any violation of applicable law or any violation of the rights of any Person,
(ii) the sole relief provided is monetary damages that are paid in full by the Indemnitor, and (iii) the Indemnitees rights are not restricted by such settlement or judgment.

Section 10.5 No Punitive, Consequential Damages. NOTWITHSTANDING ANYTHING TO THE CONTRARY, IN NO EVENT WILL EITHER PARTY OR ANY OF
ITS DIRECTORS, TRUSTEES, OFFICERS, EMPLOYEES, AGENTS OR AFFILIATES BE LIABLE TO THE OTHER PARTY FOR ANY INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, PUNITIVE OR CONSEQUENTIAL DAMAGES, WHETHER BASED UPON A CLAIM OR ACTION OF CONTRACT, WARRANTY,
NEGLIGENCE, STRICT LIABILITY OR OTHER TORT, OR OTHERWISE, ARISING OUT OF THIS AGREEMENT.

Section 10.6 Insurance.
Orexigen hereby represents that it, any Sublicensee and any Further Sublicensee shall (i) maintain product liability and other appropriate insurance (including D&O insurance) with an insurance carrier that has a minimum rating of
[* * *], which shall



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include, but not be limited to, (a) product liability insurance in the minimum amount of $[* * *] per occurrence and in the aggregate (during the time when such Person conducts human
clinical trials using the Licensed Product and/or commercializes the Licensed Product) for not less than [* * *] ([* * *]) years after expiration or earlier termination of this Agreement, (b) general liability insurance in the minimum amount of
$[* * *] in the aggregate and $[* * *] umbrella coverage, and (c) where required by statute or custom, clinical trial insurance, in the minimum amount of $[* * *] per occurrence and in the aggregate, which shall be required to be maintained at
the same level for [* * *] ([* * *]) years after the last clinical trial conducted by the applicable Person for the Licensed Product; or (ii) otherwise be self-insured in an amount consistent with industry standards for a company in a similar
position to such Person during the Term. Orexigen shall provide GSK with written notice at least [* * *] ([* * *]) days prior to any cancellation, nonrenewal or material change in the insurance described above. Orexigen shall provide a certificate
of insurance evidencing such coverage to GSK upon request. It is understood that such insurance shall not be construed to create a limit of Orexigens liability with respect to its indemnification obligations under this Article 10.

Article 11. Miscellaneous.

Section 11.1 Notices. Notices required or permitted under this Agreement will be in writing and sent by prepaid registered or certified air mail or by overnight express mail (e.g., FedEx), or by
facsimile confirmed by prepaid registered or certified air mail letter or by overnight express mail (e.g., FedEx), (provided, that failure of such confirmation will not affect the validity of such notice by facsimile to the extent the receipt of
such notice is confirmed by the act of the receiving Party (e.g., a facsimile of the receiving Party submitting its receipt of such notice)) and will be deemed to have been properly served to the addressee upon receipt of such written communication,
to the following addresses of the Parties:

If to GSK:

SROne

161 Washington Street

Suite 500

Conshohocken, PA 19428

Attention: Finance Manager

Facsimile: (610) 567-1039

and

with a copy
to:

GlaxoSmithKline

980 Great West Road

Brentford, Middlesex TW8 9GS

United Kingdom

Attention: Legal Operations, Business Development Transactions



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and

SmithKline Beecham Corporation

2301 Renaissance Boulevard

King of Prussia, PA 19406-2772

Attention: Vice President and Associate General Counsel

R&D Legal Operations
 Business Development Transactions Team

Facsimile: (610) 787-7084

If to Orexigen:

Orexigen Therapeutics, Inc.

3344 N. Torrey Pines Court, Suite 200

La Jolla, California 92037

Attention: General Counsel

Facsimile: 858-875-8650

with a copy to:

Latham & Watkins LLP

12636 High Bluff Drive, Suite 400

San Diego, CA 92130-2071

Attention: Faye H. Russell

Facsimile: 1.858.523.5450

If to Orexigens Sublicensee:

Takeda Pharmaceutical Company Limited

1-1, Doshomachi 4-Chome Chuo-ku

Osaka, 540-8645

Japan

Attention: General Manager, Global Licensing & Business Development Dept.

Facsimile: (+81) 6-6204-2328

with a facsimile copy to:

Attention: General Manager, Legal Dept.

Facsimile: (+81) 6-6204-2055

Section 11.2 Governing Law. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, without regard to principles of conflicts of laws applicable in
such jurisdiction. This Agreement and any amendment hereto may be executed in counterparts and all of such counterparts taken together shall be deemed to constitute one and the same instrument.



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Section 11.3 Miscellaneous.

(i) Binding Effect. This Agreement will be binding upon and inure to the benefit of the Parties and their
respective legal representatives, successors and permitted assigns.

(ii) Headings. Paragraph headings
are inserted for convenience of reference only and do not form a part of this Agreement.

(iii)
Counterparts. This Agreement may be executed simultaneously in two or more counterparts, each of which will be deemed an original.

(iv) Entire Agreement; Amendment; Waiver. This Agreement constitutes the entire understanding of the Parties with respect to the subject matter hereof and supersedes all previous writings and
understandings, including, without limitation, the Draft Term Sheet (Non-Binding) between the Parties dated on or about May 26, 2009, which prior writings and understandings are, to the extent not already terminated as of the Effective Date,
hereby terminated effective as of the A&R Effective Date, other than (a) the survival provisions set forth therein and (b) the Original License Agreement solely with respect to any rights and obligations in effect under the Original
License Agreement, and any Losses and/or Claims arising from or based on any activities conducted, prior to the A&R Effective Date. This Agreement may be amended, modified, superseded or cancelled, and any of the terms may be waived, only by a
written instrument executed by each Party or, in the case of waiver, by the Party waiving compliance. No waiver by any Party of any condition or of the breach of any term contained in this Agreement, whether by conduct, or otherwise, in any one or
more instances, will be deemed to be, or considered as, a further or continuing waiver of any such condition or of the breach of such term or any other term of this Agreement.

(v) No Third Party Beneficiaries; No Partnership. The terms and provisions of this Agreement shall be binding upon
and inure to the benefit of the parties, and their respective successors and assigns, subject to Section 11.3(vi), and is made solely and specifically for their benefit. No other person shall have any rights, interest or claims hereunder or be
entitled to any benefits under or on account of this Agreement as a third-party beneficiary or otherwise. Nothing contained in this Agreement will be deemed to constitute the Parties partners with each other or any Third Party.

(vi) Assignment and Successors. Neither this Agreement nor any interest hereunder may be assigned, sold,
transferred or otherwise disposed of by either Party without the prior written consent of the other Party, which consent shall not be unreasonably withheld, conditioned or delayed [* * *]. Any Sublicensee or any Further Sublicensee may only assign,
sell, transfer or otherwise dispose of its interest hereunder in compliance with Section 2.2 or with the consent of both Parties hereto, which consent shall not be unreasonably withheld, conditioned or delayed. Notwithstanding anything to the
contrary in the foregoing, either Party may assign this Agreement or any part of its rights and obligations hereunder (a) to any Affiliate of such Party, (b) in connection with a Change of Control (but only to the Person that shall Control
such Party upon the Change of Control, or an Affiliate of such Person), or to any corporation with which such Party may merge or consolidate, or to which it may transfer all or



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substantially all of its business or assets, in each of subsections (a) and (b) without obtaining the consent of the other Party [* * *], provided that any such assignee of a
Party delivers to the other Party a legally binding document committing such assignee to be bound to the obligations to such other Party under this Agreement (such delivery to be a condition to the validity of an assignment under the first proviso
in this sentence). Any attempted assignment, sale or transfer in violation of the prior sentence shall be null and void ab initio. The Parties acknowledge that the parenthetical clause of the first sentence of this
Section 11.3(vi) shall [* * *].

(vii) Force Majeure. Neither GSK nor Orexigen
will be liable for failure of or delay in performing obligations set forth in this Agreement, and neither will be deemed in breach of its obligations, if such failure or delay is due to natural disasters or any causes reasonably beyond the control
of GSK or Orexigen. When such circumstances arise, the Parties will discuss what, if any, modification of the terms of this Agreement may be required in order to arrive at an equitable solution.

(viii) Severability. If any provision of this Agreement is or becomes invalid or is ruled invalid by any court of
competent jurisdiction or is deemed unenforceable, it is the intention of the Parties that the remainder of the Agreement will not be affected.

(ix) Further Actions. Each Party agrees to execute, acknowledge and deliver such further instruments, and to do all such other commercially reasonable acts, as may be necessary or appropriate in
order to carry out the purposes and intent of this Agreement.

(x) Relationship of the Parties. It is
not the intent of the Parties to form any partnership or joint venture. Each Party will, in relation to its obligations hereunder, be deemed to be and will be an independent contractor, and nothing in this Agreement will be construed to give such
Party the power or authority to act as agent for the other Party for any purpose, or to bind or commit the other Party in any way whatsoever.

[The remainder of this page is intentionally left blank; signature page follows.]



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IN WITNESS WHEREOF, the Parties have caused this Amended and Restated License Agreement to
be executed by their duly authorized representatives as of the date first set forth above.



|                    |  |                           
|------------------- |  | --------------------------
|GLAXOSMITHKLINE LLC
|                    | 
|By:                 |  | /s/ William J. Mosher     
|                    | 
|Name:               |  | William J. Mosher         
|                    | 
|Title:              |  | Vice President & Secretary



|                    |  |                                                                                                         
|------------------- |  | --------------------------------------------------------------------------------------------------------
|GLAXO GROUP LIMITED
|                    | 
|By:                 |  | /s/ Paul Williamson                                                                                     
|                    | 
|Name:               |  | Paul Williamson                                                                                         
|                    | 
|Title:              |  | Authorized Signatory For and On Behalf of Edinburgh Pharmaceutical Industries Limited Corporate Director



|                            |  |                                             
|--------------------------- |  | --------------------------------------------
|OREXIGEN THERAPEUTICS, INC.
|                            | 
|By:                         |  | /s/ Joseph Hagan                            
|                            | 
|Name:                       |  | Joseph Hagan                                
|                            | 
|Title:                      |  | Senior Vice President, Corporate Development

[SIGNATURE PAGE TO AMENDED AND RESTATED LICENSE AGREEMENT]



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EXHIBIT A

WIRE INSTRUCTIONS

Previously provided by GSK.