Document:

nktr20191231ex1019

                                                                      Exhibit 10.19                             EMPLOYEE AGREEMENT        In consideration of my employment or continued employment by Nektar Therapeutics, its         subsidiaries or affiliates (collectively, the “Company”), I, John Northcott (name) residing at         [***]    (address)  as of the date I was first employed by Company as follows:                         1.   Entire AAgreement::  This Agreement setss   forth the completec and entire agreement  between  Company  and me  and supersedes  any and all previous  oral or written  communications, discussions  and agreements between  Company and me with respect to the  subject of this Agreement.                     2.    Employment:                     a.    Duty of LLoyalty.  During the period of my employment by the Company, I shall  devote my full time and best efforts to the business of the Company, and I shall neither pursue  any business opportunity outside the Company nor take any position with any organization other  than as authorized in writing by the Chief Executive Officer of the Company.  While employed  by the Company, I will avoid all conflicts of interest and will not compete with the Company or  undertake other acts of disloyalty.                     b.    Change in Jobs.  I agree that all of my obligations under this Agreement will   remain in full force and effect should I receive a promotion, demotion or experience a change in  job title or duties while employed by the Company.                     c.    Employment at Will.   I agree that this Agreement does not guarantee my continued  employment  with  the Company.   I acknowledge  that, unless  I enter into a written employment  agreement  with the Company that provides  for a specified period  of employment,  I am  employed  "at-will," meaning that  either the Company or I may terminate  the employment  relationship  at  any time,  for any or no reason,  with or without  cause or prior notice.                     3.    Assignment of Developments:               a.          Assignment to Company.  If at any time or times during my employment or other   association with the Company,  I shall (either alone or with others) make,  conceive,  create,  discover, invent or reduce to practice  any development  that  (i) relates to the business  of the  Company or any of the products  or services being developed, manufactured  or sold by the  Company or which  may be used in relation therewith;  or (ii) results  from tasks assigned to me by  the Company;  or (iii) results from the use  of premises  or personal  property  (whether tangible or  intangible)  owned,  leased or contracted  for by the  Company  (hereinafter  collectively referred  to  as "Developments"), then  all such Developments  and the benefits thereof are and shall  immediately become  the sole and absolute property  of the Company and its assigns,  as works  made for hire or otherwise.   I shall promptly disclose to the Company (or any persons  designated  by it) each such Development.   I hereby assign  all rights (including, but not limited to, rights to  inventions, patentable  subject matter, copyrights and trademarks)  I may have or may acquire in  the Developments,  as well  as all benefits and/or rights resulting therefrom, to the Company and  its assigns without  further compensation  and shall communicate, without  cost or delay, and  without  disclosing to others the same, all available information relating thereto  (with all necessary  plans and models) to the Company.                     b.    Req uirement to Provide Assistance.  I agree to assist the Company, or its  designee, at the Company's expense, in every proper way to secure the Company's rights in the 

 

Developments and any copyrights, patents, trademarks, and trade secret rights or other  intellectual property rights in connection with any such Developments in any and all countries,  including the disclosure to the Company of all pertinent information and data with respect thereto,  the execution of all applications, specifications, oaths, assignments and all other instruments  which the Company shall deem necessary in order to apply for and obtain such rights and in order  to assign and convey to the Company, its successors, assigns, and nominees the sole and exclusive  rights, title and interest in and to such Developments, and any copyrights, patents, trademark and  other intellectual property rights relating thereto.  I further agree that my obligation to execute or  cause to be executed, when it is in my power to do so, any such instrument or papers shall  continue after the termination of this Agreement.  If the Company is unable, because of my  mental or physical incapacity or for any other reason, to secure my signature to apply for or to  pursue any application for any United States or foreign patents or copyright registrations  covering Developments or original works of authorship assigned to the Company as above, then I  hereby irrevocably designate and appoint the Company and its duly authorized officers and  agents as my agent and attorney in fact, to act for and in my behalf and stead to execute and file  any such applications and to do all other lawfully permitted acts to further the prosecution and  issuance of letters patent or copyright registrations thereon with the same legal force and effect as  if executed by me.                     c.    Works Made For Hire.  I will promptly  disclose to the Company all material which  I produce,  compose or write, individually or in collaboration  with others, which arises out of work  delegated  to me by the Company.   I agree that all such material  constitutes a work for hire, and at  the expense of the Company,  I will assign to the Company all my interest in such copyrightable  material  and will sign all papers  and do all other acts necessary to assist the Company to obtain  copyrights on such material in any and all countries.                     d.    Ongoing Notice Obligation.   I agree that for a period  of one (1) year following the  termination  of my employment  for any reason,  I will notify the Company immediately  of any  and all creations, discoveries,  inventions  or other developments made by me (either alone or with  others) that relate to the business of the Company or relate to research and development in which I  was involved  during the course of my employment by the Company.  Any such creation,  discovery,  invention  or other development  relating to the Company's business made by me  (either alone or with others) within one (1) year following the termination  of my employment shall  be presumed  to be owned by the Company.                e.         Inventions Not Assigned to Company.   I understand  and acknowledge that the  assignment of Developments under this Agreement  does not apply to an invention which qualifies  fully for protection  under section 2870 California Labor Code section, a copy of which is attached  as Appendix A, which pertains to any rights I may have acquired in connection with an invention,  discovery or improvement  that was developed entirely on my own time for which no equipment,  supplies, facilities or trade secret information  of the Company was used and (a) that does not relate  directly or indirectly to the business of the Company or to the Company's actual or demonstrably  anticipated research or development, or (b) that does not result from any work performed by me  for the Company.                     f.        Disclosure of Prior Inventions.  I represent that the creations, discoveries,  inventions or other developments identified in Appendix B attached hereto ("Prior  Developments"), if any, comprise all the Prior Developments that I made or conceived prior to  my employment by the Company, which Prior Developments are excluded from this Agreement.  I understand that it is only necessary to list the title of such Prior Developments and the purpose  thereof, but not details of the Prior Development itself.  IF THERE ARE ANY SUCH 

 

DEVELOPMENTS TO BE EXCLUDED, THE UNDERSIGNED SHOULD INITIAL HERE;  OTHERWISE IT WILL BE DEEMED THAT THERE ARE NO SUCH EXCLUSIONS.                     4.    Nondisclosure   and Nonuse  of Confidential   Information:   I shall not at any time,  whether  during or after the termination  of my employment,  reveal  to any person  or entity any  Confidential  Information  except to employees  of the Company who need to know  such  Confidential  Information  for the purposes  of their employment, or as otherwise  authorized  by the  Company  in writing.   The term  "Confidential  Information"  shall include any information  concerning the organization, business  or finances of the Company or of any third party which the  Company is under  an obligation to keep confidential  that is maintained  by the Company  as  confidential.   Such Confidential  Information  shall include, but is not limited to, trade secrets or  confidential  information  respecting methods,  scientific data or experiments,  clinical  data, know-  how, techniques,  systems, processes,  specifications,  blueprints,  formulae, devices,  models,  software programs,  works  of authorship,  customer  lists, customer  information,  financial  information, pricing or commission  information,  business plans, projects,  plans  and proposals.   I  shall keep confidential  all matters entrusted  to me and shall not use or attempt to use any  Confidential  Information  except as may be required  in the ordinary  course of performing my  duties as an employee of the Company,  nor shall I use any Confidential  Information  in any manner  which may injure or cause loss or may be calculated  to injure or cause loss to the Company,  whether  directly or indirectly.    I further recognize that  Confidential  Information  may be embodied  in hard-copy  documents,  electronic records  and also the content of my memories  of information  that I had  access to during my employment with the Company.   Some of the Confidential  Information  may be further protected  under  California law as a trade  secret as that term is defined  in the Uniform  Trade Secrets Act  (Civil Code section 3426.1011)                     5.    Nonsolicitation   of Customers  and Employees:   I agree that the Company has  invested  substantial time, effort and expense in compiling its confidential  and trade  secret  information  and in assembling its present personnel  and customers.   In order to protect  the  confidentiality  of the Company's  sensitive information,  I agree that, during my employment  and  for one (1) year thereafter,  I shall not do the following:                     a.    directly or indirectly  solicit  in any way  any customer of the Company with the use  or  assistance  of Confidential  Information  of the Company  that  I obtained  during my  employment  for the purpose  of engaging in or assisting in soliciting business  from that  customer;                     b.    solicit any person who  is then in the employ of the Company to leave the employ  of the Company;  or                     c.          aid, assist or counsel any other person,  firm or corporation to do any of the above.                     6.    Return of Property:  I shall keep on Company's premises (except when required  elsewhere in connection with the conduct of Company's business) and shall deliver to Company  upon termination of my employment all writings related to the business of Company, and all  documents, equipment, materials and other personal property belonging to Company.  I further  agree not to make or retain any copy, duplication, facsimile, reproduction or replication of any of  the foregoing except as necessary to perform my duties as an employee of the Company. This  provision pertains to hard copy documents and any and all electronic records.                     7.    No Violation Of Prior Trade Secret Or Non-Competition  Agreements:  I represent  that the performance  of all the terms of this Agreement  as an employee  of this Company will not  conflict with, and will not breach,  any other development  assignment  agreement,  confidentiality 

 

 agreement,  employment  agreement or non-competition  agreement to which  I am or have been  a   party.   To the extent that I have confidential  information or materials  of any former employer of   mine, I acknowledge that the Company has directed me to not disclose such confidential   information  or materials  to the Company or any of its employees,  and that the Company   prohibits  me from using  said confidential information or materials in any work that  I may   perform for the Company,  and I will not bring with me to the Company, and will not use or   disclose any confidential,  proprietary  information, or trade  secrets acquired by me prior to my   employment with the Company.   I will not disclose to the Company or any of its employees,  or   induce the Company or any of its employees  to use,  any confidential  or proprietary  information   or material belonging to any previous  employers or others, nor will I bring to the Company or   use in connection with my work for the Company copies of any software,  computer files, or any   other copyrighted  or trademarked  materials  except those owned by or licensed to the Company.   I am not a party to any other agreement that will interfere with my full compliance with this   Agreement.   I further agree not to enter into any agreement, whether written or oral, in conflict   with the provisions  of this Agreement.           8.    Choice of Law:  This Agreement  shall be construed  and governed by the laws of   the State of California.           9.    No Waiver:   The waiver  of any breach of this Agreement  shall not constitute a   waiver of subsequent similar of dissimilar breaches  of this Agreement,  or a waiver of any of the   obligations  contained herein.           10.   Assignment:   The Company  shall have the right to assign this Agreement  to its   successors  and assigns, and all covenants and agreements hereunder  shall inure to the benefit  of   and be enforceable by said successors  and assigns.           11.   Right to Notify:   I recognize the right of Company to notify any third party of the   existence of this Agreement  and/or its provisions  and/or my agreeing to it.           12.   Severability:   Should a provision  or part of a provision  of this Agreement be   found as a matter or law to be invalid, such finding shall not have the effect of invalidating the   remainder of this Agreement  and the provision  or part thereof as to which  such finding of   invalidity is made shall be interpreted  so as to be ineffective only to the extent of such invalidity    without invalidating the remainder of such provision or part thereof or any of the other provisions        of this Agreement.            13.      Breach:  I agree that any breach of this Agreement by me will cause irreparable   damage to the Company and that in the event of such breach the Company shall have, in addition   to any and all remedies of law, the right to an injunction, specific performance or other equitable   relief to prevent the violation of my obligations hereunder.    EMPLOYEE:    Signed: /s/ John Northcott    Name:   John Northcott  Dated: November 26, 2019     

 

Nektar Therapeutics    By:  /s/ Dorian Hirth    Title: Sr  Vice President, Human Resources    Dated: 12/4/2019                                                                   Nektar Therapeutics - Confidential                                                                                                        May 2009                                        APPENDIX  A       Section  2870  of  California  Labor  Code:  Application  of  provision  providing  that  employee    shall assign or offer to assign rights in invention  to employer.             a.    Any provision  and employment  agreement  which provides that an employee shall    assign, or offer to assign, any of his or her rights in an invention to his or her employer  shall not    apply to an invention that the employee developed  entirely on his or her own time without  using    the employer's equipment,  supplies, facilities or trade secret information  except for those    inventions that either:                   1     Relate at the time of conception  or reduction  to practice ·of the invention  to                      the  employer's  business,  or  actual  or  demonstrably  ariticipated  research  or                      development of the employer; or                   2     Result from any work performed  by the employee for the employer.             b.    To the extent a provision  in an employment  agreement purports to require an    employee to assign an invention otherwise excluded from being required  to be +assigned  under    subdivision (a), the provision  is against the public policy of this  state and is unenforceable.       Nektar Therapeutics - Confidential                                                                                                       May 2009 

 

Nektar Therapeutics – Confidential                                                 APPENDIX B                                      PRIOR INVENTIONSnktr20191213ex1035

                                                                            Exhibit 10.35     [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted from this            exhibit in accordance with the rules of the Securities and Exchange Commission.                                    AMENDMENT NO. 1                      TO STRATEGIC COLLABORATION AGREEMENT         This AMENDMENT NO. 1 (this “Amendment”) to the Agreement (as defined below) is entered  into as of January 9, 2020 (the “Amendment Effective Date”) by and between Nektar Therapeutics, a  Delaware corporation, headquartered at 455 Mission Bay Boulevard South, Suite 100, San Francisco, CA   94158 (“Nektar”) and Bristol-Myers Squibb Company, a Delaware corporation, with offices at 430 E.  29th  Street,  14th  floor,  New  York,  NY   10016  (“BMS”).   Nektar  and  BMS  may  be  referred  to  herein  individually as a “Party,” or collectively as the “Parties.”                                         RECITALS          WHEREAS,  the  Parties  have  entered  into  a  Strategic  Collaboration  Agreement  dated  as  of  February 13, 2018 and effective as of April 3, 2018 (the “Agreement”);          WHEREAS,  the  Parties  have  agreed  to  a  revised  version  of  the  Joint  Development  Plan  that  supersedes and replaces any prior versions thereof, including the initial Joint Development Plan attached to  the Agreement as Schedule 3.1;          WHEREAS, as a result of their agreement on a revised Joint Development Plan, the Parties wish  to amend the list of Collaboration Therapies attached to the Agreement as Schedule 1.43; and          WHEREAS,  the  Parties,  pursuant  to  Section  17.9  of  the  Agreement,  wish to  formalize  their  agreement on the revised Joint Development Plan and agree on certain additional amendments pursuant to  the terms and conditions hereof.          NOW, THEREFORE, in consideration of the foregoing premises and the mutual promises and  covenants contained herein, the receipt and sufficiency of which is hereby acknowledged, the Parties agree  as follows:   1.     DEFINITIONS          The terms in this Amendment with initial letters capitalized that are not defined herein shall have  the meaning set forth in the Agreement.   2.    AMENDMENTS          2.1   Joint Development Plan                (a)    Pursuant to Sections 3.1(b), 3.6(b) and 3.6(c) of the Agreement, the Parties, on the  basis of a meeting of the JDC held on [***], and through other discussions held in accordance with the  Agreement  have  agreed  to  a  revised  Joint  Development  Plan.   The  revised  Joint  Development  Plan,  effective as of the Amendment Effective Date, is attached hereto as Appendix A.  The Parties hereby waive  the requirement to have the revised Joint Development Plan attached hereto as Appendix A approved at a  meeting of the JDC.  This revised Joint Development Plan replaces and supersedes, as of the Amendment  Effective Date, the initial Joint Development Plan attached as Schedule 3.1 to the Agreement.                 (b)    As a result of their agreement on this revised Joint Development Plan, the Parties  are hereby released from any and all obligations or restrictions in respect of any of the Initial Trials that are     ACTIVE/102462316.2   

 

not listed in the revised Joint Development Plan attached hereto as Appendix A (including relating to the  conduct thereof).                 (c)    Subject to Section 2.1(g), for each of the Collaboration Studies contemplated in  the  revised  Joint  Development  Plan,  Appendix  A  sets  forth,  for each  Collaboration  Study,  either  its  Diligence Date or a confirmation that the Diligence Date has been met, provided that such Diligence Dates  shall remain subject to Allowable Delays.                 (d)    For purposes of this Amendment and to the actual knowledge of BMS’ [***], BMS  is  not  aware  of  any  circumstance  that  would  justify  to  delay,  on  the  basis  of  the  application  of  the  Commercially  Reasonable  Efforts  standard  of  the  Agreement,  the commencement  (and  solely  the  commencement), by the applicable Diligence Date, of any of the Collaboration Studies referred to in the  Joint Development Plan attached as Appendix A that has not started as of the Amendment Effective Date.   For purposes of this Amendment and to the actual knowledge of Nektar’s [***], Nektar is not aware of any  circumstance that would justify to delay, on the basis of the application of the Commercially Reasonable  Efforts standard of the Agreement, the commencement (and solely the commencement), by the applicable  Diligence Date, of any of the Collaboration Studies referred to in the Joint Development Plan attached as  Appendix A that has not started as of the Amendment Effective Date.                (e)    As a result of their agreement on the revised Joint Development Plan, the Parties  agree to a revised Schedule 1.43 (Collaboration Therapies) to the Agreement.  Such revised Schedule 1.43,  attached hereto as Appendix C, replaces and supersedes, as of the Amendment Effective Date, the initial  version of Schedule 1.43 attached to the Agreement.  For clarity, as of the Amendment Effective Date, the  restrictions set forth in Section 7.3(d) of the Agreement will no longer apply to any Collaboration Therapy  that is not listed in the revised Schedule 1.43 attached hereto as Appendix C.  For additional clarity, the  restrictions set forth in Section 7.3(d) of the Agreement will apply to first line non-small-cell lung cancer  Collaboration  Therapy  even  if  there  is,  as  of  the  Amendment  Effective  Date,  no  Collaboration  Study  associated with that Collaboration Therapy.                (f)    BMS shall have the right, at its sole discretion, to terminate co-funding of its pro  rata share of the Development Costs for the Adjuvant Melanoma Collaboration Study by notice in writing  to Nektar in the event that the Metastatic Melanoma Collaboration Study fails to meet the primary endpoint  of progression-free survival (the “Adjuvant Melanoma Co-Funding Termination Right”).  In the event  that any primary or co-primary endpoint is not reached in the Metastatic Melanoma Collaboration Study,  the Parties, with the understanding that the health and welfare of patients is of foremost importance, agree  to meet and confer to discuss whether there is a need to inform patients, physicians or study sites involved  in the Adjuvant Melanoma Collaboration Study of such endpoints not having been reached or other relevant  information in the Metastatic Melanoma Collaboration Study, and if so, the means and timeframe to do so.   In the event BMS duly exercises its Adjuvant Melanoma Co-Funding Termination Right, Nektar shall have  the  right,  in  its  sole  discretion,  to  continue  the  Adjuvant  Melanoma  Study  as  a  Combined  Therapy  Independent Study pursuant to the Agreement.                (g)    For the avoidance of doubt, notwithstanding anything herein or in the Agreement  to the contrary, nothing in this Amendment or the Agreement should be read or construed as creating any  obligation on either Party to agree to conduct any Phase III Study or registrational Clinical Trial of a [***].   The gating criteria included in Appendix A in this respect are for guidance purposes only.                [***]      [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted    from this exhibit in accordance with the rules of the Securities and Exchange Commission.                                                                                     Page 2   

 

       2.2   Release  and Waiver.   EACH  PARTY  HEREBY  FULLY  AND  IRREVOCABLY  RELEASES AND WAIVES ANY CLAIM, WHETHER KNOWN OR UNKNOWN, IT HAS OR MAY  HAVE FROM THE BEGINNING OF TIME TO THE AMENDMENT EFFECTIVE DATE AGAINST  THE OTHER PARTY ARISING OUT OF, OR RELATING TO, (A) ANY FAILURE BY SUCH OTHER  PARTY TO CONDUCT ANY OF THE INITIAL TRIALS OR (B) ANY OF THE INITIAL TRIALS NOT  HAVING MET THEIR DILIGENCE DATE, INCLUDING AS SET FORTH IN SECTION 3.2(A) OF  THE AGREEMENT.          2.3   Additional Milestone Payments           (a) Additional,  Non-creditable  Milestone  Payment.   Within  [***]  following  the  achievement of the first patient, first visit in the first Phase III Study of a Combined Therapy consisting of  a Product and the BMS Compound that is conducted as a Combined Therapy Collaboration Study (and not  an Independent Study) in adjuvant melanoma (the “Additional Melanoma Milestone”), BMS shall pay, or  cause to be paid, to Nektar an amount of twenty-five million U.S. Dollars ($25,000,000) (the “Additional  Melanoma Milestone Payment”).  The Additional Melanoma Milestone Payment payable pursuant to this  Section 2.3(a) will be non-refundable and non-creditable and is in addition to all other payments that are,  or  may  be  due,  to  Nektar  under  the  Agreement  (as  amended).   The  Additional  Melanoma  Milestone  Payment shall be payable only one time regardless of the number of products that achieve such Additional  Melanoma Milestone and regardless of the number of Indications for which such Additional Melanmoa  Milestone is achieved.             (b) Additional, Creditable Milestone Payments.                         (i)    Additional  MIBC  Milestone  Payment.   Within  [***]  following the  achievement of the first patient, first visit in the first Phase III Study of a Combined Therapy consisting of  a Product and the BMS Compound that is conducted as a Combined Therapy Collaboration Study (and not  an Independent Study) in Muscle Invasive Bladder Cancer (the “Additional MIBC Milestone”), BMS shall  pay,  or  cause  to  be  paid,  to  Nektar  an  amount  of  twenty-five  million  U.S.  Dollars  ($25,000,000)  (the  “Additional MIBC Milestone Payment”).  The Additional MIBC Milestone Payment payable pursuant to  this Section 2.3(b)(i) will be non-refundable, but will be fully creditable against any future Development  Milestone Payment(s) payable by BMS to Nektar pursuant to Section 9.2(b) of the Agreement, until the full  amount of such Additional MIBC Milestone Payment shall have been applied to Development Milestone  Payments.  The Additional MIBC Milestone Payment shall be payable only one time regardless of the  number  of  Products  that  achieve  such  Additional  MIBC  Milestone and  regardless  of  the  number  of  Indications for which such Additional MIBC Milestone is achieved.                          (ii)  Within [***] following the achievement of the first patient, first visit in  the first Phase III Study of a Combined Therapy consisting of a Product and the BMS Compound that is  conducted as a Combined Therapy Collaboration Study (and not an Independent Study) in First Line Non- Small-Cell Lung Cancer (the “Additional Lung Milestone”), BMS shall pay, or cause to be paid, to Nektar  an amount of seventy-five million U.S. Dollars ($75,000,000) (the “Additional Lung Milestone Payment”).   The Additional Lung Milestone Payment payable pursuant to this Section 2.3(b)(ii) will be non-refundable,  but  will  be  fully  creditable  against  any  future  Development  Milestone  Payment(s)  payable  by  BMS  to  Nektar  pursuant  to  Section  9.2(b)  of  the  Agreement,  until  the  full  amount  of  such  Additional  Lung  Milestone Payment shall have been applied to Development Milestone Payments.  The Additional Lung  Milestone Payment shall be payable only one time regardless of the number of Products that achieve such  Additional Lung Milestone and regardless of the number of Indications for which such Additional Lung  Milestone is achieved.  For the avoidance of doubt, notwithstanding anything herein or in the Agreement       [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted      from this exhibit in accordance with the rules of the Securities and Exchange Commission.                                                                                    Page 3   

 

to the contrary, nothing in this Amendment or the Agreement should be read or construed as creating any  obligation  on  either  Party  to  agree  to  conduct  any  Phase  III  Study  or  registration  Clinical  Trial  of  the  Combined Therapy in [***] as a Combined Therapy Collaboration Study.          2.4   Combined Therapy Collaboration Studies Expenses.  Schedule 6.3 of the Agreement is  replaced in its entirety by the new version attached to this Amendment as Appendix D.          2.5   Right of Cross Reference. Section 4.2(b)(v) of the Agreement is replaced in its entirety  by the following:                       “(v)   to  the  extent  necessary  for  the  conduct  of  any  Collaboration  Study  or               Independent Study or BMS’s filing of a BLA or supplemental BLA as set forth in Section               10.1(b),  providing  BMS  a  Right  of  Cross-Reference  to  the  relevant  Regulatory               Documentation, provided that,  such  Right of  Cross-Reference  shall  terminate  upon  the               expiration or termination of this Agreement for purposes of conducting any new Clinical               Trials, except that in the case of termination for a Material Safety Issue pursuant to Section               16.4,  such  Right  of  Cross-Reference  shall  remain  in  effect  solely (A) to the extent               necessary  to  permit  BMS  to  comply  with  any  outstanding  obligations  required  by  a               Regulatory  Authority  and/or  Applicable  Law  or  (B)  as  necessary to  permit  BMS  to               continue  to  dose  subjects  enrolled  in  each  Collaboration  Study or  Independent  Study               through completion of the applicable Protocol if required by the applicable Regulatory               Authority(ies) and/or Applicable Laws;”          2.6   Reimbursement  for  Opt-Out  Development  Costs.   Section  7.4  of  the  Agreement  is  replaced in its entirety by the following:                        “7.4  Reimbursement for Opt-Out Development Costs.  If a Monotherapy               Independent  Study  or  Combined  Therapy  Independent  Study  results  in  Regulatory               Approval or a Label expansion of a BMS Asset or Nektar Asset (including the Nektar               Compound), the non-funding Party shall reimburse the funding Party for the non-funding               Party’s allocated share of Opt-Out Development Costs incurred by the funding Party for               the applicable Monotherapy Independent Study or Combined Therapy Independent Study               (using the principles set forth in Sections 5.3(c)(i), 6.2 and 6.3) for which the non-funding               Party  would  have  been  responsible  had  such  Independent  Study  been  a  Collaboration               Study, plus an amount equal to either (i) [***] of such reimbursement in the event that the               applicable  Combined  Therapy  Independent  Study  studies  the  Combined  Therapy  of  a               Product and the BMS Compound (whether or not other compounds are included in such               study), or (ii) [***] of such reimbursement in all other cases.  Such reimbursed Opt-Out               Development Costs (and the [***] or [***], as applicable, additional reimbursement for               such  Independent  Study)  shall  be  subject  to  the  reconciliation procedures  set  forth  in               Section 9.7 but shall not be subject to the Development Cost Cap.”          2.7    Independent Studies.  Appendix B hereto includes a list of Independent Studies currently  being conducted or planned to be initiated by a Party.         2.8    [***]           2.9    [***]          [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted       from this exhibit in accordance with the rules of the Securities and Exchange Commission.                                                                                    Page 4   

 

       2.10  Governance.  The Parties agree that Allowable Delays shall include the time between the  expiration  of  any  contractually  agreed  timeframefor  the  provision by one Party to the other Party of  information, comments or Study Data and the actual provision thereof.   3.     PUBLICITY          Upon execution of this Amendment, the Parties will issue a press release the contents of which is  as attached hereto as Appendix E.  The aforementioned press release will be issued within [***] before the  opening of U.S. based stock market trading on [***].    4.     MISCELLANEOUS          4.1   This Amendment shall become effective on the Amendment Effective Date.          4.2   Unless  and  to  the  extent  expressly  amended  by  this  Amendment,  all  the  terms  and  conditions of the Agreement shall remain in full force and effect.          4.3   In the event of a conflict between the terms of this Amendment (or any attachments thereto)  and the terms of the Agreement, the terms of this Amendment (including its attachments) shall prevail.          4.4   The headings used in this Amendment have been inserted for convenience of reference  only and do not define or limit the provisions hereof.          4.5   This Amendment may be signed in any number of counterparts (facsimile and electronic  transmission included), each of which shall be deemed an original, but all of which shall constitute one and  the same instrument.          4.6   This Amendment and all claims relating to or arising out of this Amendment or the breach  thereof shall be governed and construed in accordance with the internal laws of the State of New York,  USA, excluding any choice of law rules that may direct the application of the laws of another jurisdiction.  The United Nations Convention on Contracts for the International Sale of Goods shall not apply to this  Agreement.  Further, Disputes arising out of this Amendment, other than a JDC Dispute, JCC Dispute, JFC  Dispute or JMC Dispute or a Publication Dispute or a dispute as to whether a Material Safety Issue exists,  shall be resolved in accordance with Section 15.1 of the Agreement.  No part of this Amendment changes  the rights and obligations of the Parties under Article 15 of the Agreement.          4.7   This Amendment and the Agreement (as amended by the Amendment) constitute the entire  understanding  between  the  Parties  with  respect  to  the  subject  matter  hereof,  and  supersede  all  prior  agreements whether oral or written.  No amendment, modification, waiver, release or discharge to this  Amendment or the Agreement shall be binding upon the Parties unless in writing and duly executed by  authorized representatives of both Parties.          4.8   This Amendment has been prepared jointly and shall not be strictly construed against either  Party. No presumption as to construction of this Amendment shall apply against either Party with respect  to any ambiguity in the wording of any provision(s) of this Amendment irrespective of which Party may be  deemed to have authored the ambiguous provision(s).                                                                                          (signature page follows)       [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted      from this exhibit in accordance with the rules of the Securities and Exchange Commission.                                                                                    Page 5   

 

       IN WITNESS WHEREOF, the Parties, intending to be legally bound hereby, have caused this  Amendment to be executed by their duly authorized representatives as of the Amendment Effective Date.                                              For and on behalf of Nektar Therapeutics:                                                                                      Signature:   /s/ Howard W. Robin                                            Title:       President and CEO                                            Date:        01/09/20                                                                                                                                                                            For and on behalf of Bristol-Myers Squibb Company:                                                                                      Signature:   /s/ Charles Bancroft                                            Title:       Executive  VP,  Strategy  and  Business                                                       Development                                            Date:        01/09/20                              Signature page to Amendment No. 1 to the Strategic Collaboration Agreement   ACTIVE/102462316.2   

 

                                                        APPENDIX A                                                 JOINT DEVELOPMENT PLAN                                                  (Effective as of January 9, 2020)                                                                                           Number                         Lead    Tumor    Phase      Patient Population                   Study Design                             Diligence Date                                                                                          Patients                      Party               3     1L metastatic melanoma    Bempeg + Nivo vs. Nivo                       764          Achieved       BMS  Melanoma               3     Adjuvant melanoma         Bempeg + Nivo vs. Nivo                       1100           [***]       NKTR              3     1L metastatic RCC doublet   Bempeg + Nivo vs. TKI                      600          Achieved      NKTR                                              Phase 1.  Dose escalation cohort: Nivo +                                                                                            6-20           [***]        BMS                                               Bempeg + axitinib                                               Phase 2, gated study.  Expansion cohort: Nivo +                                               Bempeg + Axitinib vs Nivo + Axitinib (gated upon     RCC                                                                                     80            [***]        BMS              1/2/3  RCC triplet               acceptable safety profile from dose escalation (1)                                               prior to initiation)                                              Phase 3, gated study.  [***]                 960            [***]        BMS                2     1L metastatic UC          Bempeg + Nivo                                190          Achieved      NKTR   Bladder          Muscle-invasive bladder                                               Bempeg + Nivo vs Nivo                        540            [***]        BMS               3     cancer              1/2A   Pediatric study           Bempeg + Nivo                                [***]          [***]        BMS    Other       1    Safety study - Japan Phase 1  Bempeg + Nivo                             20          Achieved       BMS                1    Safety study - [***]      Bempeg + Nivo                                [***]          [***]        BMS  Bempeg = Bempegaldesleukin; Nivo = Nivolumab PIVOT-02 – Parties have agreed to stop additional enrollment, continue to provide patient follow up and conclude the study.                                                                                                                  [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted                        from this exhibit in accordance with the rules of the Securities and Exchange Commission.       

 

                                                          APPENDIX B                                                       INDEPENDENT STUDIES                                                         (as of January 9, 2020)   Tumor              Study           Lead      Trial Design                     End Point(s)    FPFV          Number of Patients                                     Party  Non-small cell lung PROPEL -       Nektar    Bempeg + Pembrolizumab           Safety, ORR     Achieved      Approximately 135   cancer (NSCLC)     NSCLC Phase 1/2   Non-small cell lung NSCLC Dose     BMS       Nivo + Bempeg 0.009 mg/kg vs.    ORR             [***]         180  cancer (NSCLC)     Optimization              Nivo + Bempeg 0.006 mg/kg vs. Nivo +                     Phase 1/21                Ipi Multiple Solid Tumor Reveal Phase 1/2  Nektar  NKTR-262 + bempeg and in       Safety, ORR     Achieved      Phase 1:  Approximately 48  Indications                                  combination with Bempeg + Nivo                                 Phase 2:  Approximately 400   Squamous Cell Head Phase 1/2       Pfizer    Avelumab in combination with bempeg Safety, ORR, PSA Achieved  20-40 for each combination  and Neck Cancer                              with or without talazoparib or   response rate                                               enzalutamide  Metastatic Colorectal  and Prostate Cancer  Unresectable or    Phase 2         Bioxcel   BXCL701 in combination with avelumab Safety, ORR [***]         Approximately 52  Metastatic Pancreatic                        and bempeg  Adenocarcinoma  Locally advanced or Phase 2        Vaccibody  VB10.NEO or VB10.NEO plus bempeg   Safety, ORR  [***]         Approximately 50  metastatic solid  tumors including  melanoma, NSCLC,  clear RCC, urothelial  cancer or SCCHN  Sarcoma            IST             IST by    Bempeg + Nivo                    ORR             Achieved      Approximately 85                                     MSKCC [***]   Bempeg = Bempegaldesleukin  Ipi = Ipilimumab  Nivo = Nivolumab                                  [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted                      from this exhibit in accordance with the rules of the Securities and Exchange Commission.       

 

                                                                          Execution Version                                                                                                                                                                              APPENDIX C                                       SCHEDULE 1.43                               COLLABORATION THERAPIES    No.   Lines and Indications                         MOAs / Targets*                                                        IL-2 + PD(L)-1   1     1L or later non-small-cell lung cancer                                                       [***]    2     1L melanoma                                   IL-2 + PD(L)-1    3     Adjuvant melanoma                             IL-2 + PD(L)-1                                                        IL-2 + PD(L)-1   4     1L renal cell carcinoma                                                       [***]    5     1L bladder cancer                             IL-2 + PD(L)-1     6     Muscle invasive bladder cancer                IL-2 + PD(L)-1      * For purposes of this Schedule:      -  PD-1 and PD-L1 are considered as the same mechanism of action (“MOA”) for purposes of this        Agreement; and     -  IL-2 refers to any IL-2 Agonist                                                                  [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted        from this exhibit in accordance with the rules of the Securities and Exchange Commission.    

 

                                                                          Execution Version                                                                                                                                APPENDIX D                                       SCHEDULE 6.3     COMBINED THERAPY COLLABORATION STUDY DEVELOPMENT COST ALLOCATION    Combined Therapy Collaboration Study Development Cost Allocation:    Combinations with Products                           Nektar      BMS         Third Party    Doublet  with  the  BMS  Compound  or  any  other  single  BMS 32.5%  67.5%  -   Asset or Third Party Asset sourced by BMS    Doublet  with  any  other  Nektar  Asset  or  Third  Party  Asset 82.5%  17.5%  -   sourced by Nektar    Triplet  with  2  BMS  Assets  (which  may  include  the  BMS 22%  78%       -   Compound)    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]    [***]                                                [***]       [***]       [***]   [***]   In the event that a Collaboration Study includes multi-arm comparative studies that draw on more than one  combination described in the above table (e.g., a doublet with a BMS Compound plus a triplet with 1 BMS  Asset plus 1 Nektar Asset) the Development Cost allocations between Nektar and BMS shall be a blended  rate based [***].  Using the example from the prior sentence, [***]              [***] Certain confidential portions (indicated by brackets and asterisks) have been omitted         from this exhibit in accordance with the rules of the Securities and Exchange Commission.    

 

                                     Execution Version                                                      APPENDIX E   Press Release                    (See attached)                                                                                                                                                                                                                                                   

 

                                                                          Execution Version                                                                                                                                                                                                                                     Jan 10, 2020  Nektar Therapeutics and Bristol-Myers Squibb Amend  Strategic Collaboration Agreement for bempegaldesleukin  Plus Opdivo (nivolumab)    SAN FRANCISCO & NEW YORK--(BUSINESS WIRE)--Jan. 10, 2020-- Nektar  Therapeutics (Nasdaq:NKTR) and Bristol-Myers Squibb Company (NYSE:BMY) announced  today the companies have agreed to a new joint development plan to advance  bempegaldesleukin (bempeg) plus Opdivo (nivolumab) into multiple new registrational trials.  The revision to the strategic collaboration agreement includes a new joint development plan  under which Nektar and Bristol-Myers Squibb will expand the active clinical development  program for bempeg plus nivolumab from three ongoing registrational trials in first-line  metastatic melanoma, first-line cisplatin-ineligible metastatic urothelial cancer and first-line  metastatic renal cell carcinoma (RCC) to include two additional registrational trials in adjuvant  melanoma and in muscle-invasive bladder cancer. In addition, a Phase 1/2 dose escalation and  expansion study will be initiated to evaluate bempeg plus nivolumab in combination with axitinib  in first-line RCC in order to support a future registrational trial. The costs for these studies will  be shared based upon the cost-sharing outlined in the terms of the original collaboration  agreement. Also as part of the new strategic collaboration agreement, Bristol-Myers Squibb will  independently conduct and fund a Phase 1/2 dose optimization and expansion study in first-line  non-small-cell lung cancer with bempeg and nivolumab.  “Bristol-Myers Squibb and Nektar view bempeg as an important asset and IL-2 as an important  target,” said Fouad Namouni, M.D., head of oncology development, Bristol-Myers Squibb. “We  look forward to expanding the registrational program currently underway for bempeg and are  committed to the development of potential new combination therapies to address the unmet  needs of patients living with cancer.”  “We are pleased to move forward with this new set of registrational trials for bempeg, including  the addition of an important Phase 3 study in adjuvant melanoma which builds on the existing  metastatic melanoma study and our Breakthrough Therapy Designation,” said Nektar President  & CEO Howard W. Robin. “We now have a comprehensive plan to target multiple indications  and have the opportunity to continue to collaborate on development with other companies in  indications outside of those in the BMS and Nektar joint development program.”  About Opdivo  Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to  uniquely harness the body’s own immune system to help restore anti-tumor immune response.  By harnessing the body’s own immune system to fight cancer, Opdivo has become an important  treatment option across multiple cancers.  Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific  expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across  all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical    

 

                                                                          Execution Version                                                                                           development program has treated more than 35,000 patients. The Opdivo trials have  contributed to gaining a deeper understanding of the potential role of biomarkers in patient  care, particularly regarding how patients may benefit from Opdivo across the continuum of PD- L1 expression.  In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory  approval anywhere in the world. Opdivo is currently approved in more than 65 countries,  including the United States, the European Union, Japan and China. In October 2015, the  Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology  combination to receive regulatory approval for the treatment of metastatic melanoma and is  currently approved in more than 50 countries, including the United States and the European  Union.  About Yervoy  Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds  to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of  CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation  and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also  reduce T-regulatory cell function, which may contribute to a general increase in T-cell  responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food  and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with  unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic  melanoma in more than 50 countries. There is a broad, ongoing development program in place  for Yervoy spanning multiple tumor types.   U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®  OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with  unresectable or metastatic melanoma.   OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment  of patients with unresectable or metastatic melanoma.   OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell  lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with  EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved  therapy for these aberrations prior to receiving OPDIVO.   OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic small cell lung  cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line  of therapy. This indication is approved under accelerated approval based on overall response  rate and duration of response. Continued approval for this indication may be contingent upon  verification and description of clinical benefit in confirmatory trials.   OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell  carcinoma (RCC) who have received prior anti-angiogenic therapy.   OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment  of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma  (RCC).   OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin  lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell  transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy  that includes autologous HSCT. This indication is approved under accelerated approval based  on overall response rate. Continued approval for this indication may be contingent upon  verification and description of clinical benefit in confirmatory trials.    

 

                                                                          Execution Version                                                                                           OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic  squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after  platinum-based therapy.   OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or  metastatic urothelial carcinoma who have disease progression during or following platinum- containing chemotherapy or have disease progression within 12 months of neoadjuvant or  adjuvant treatment with platinum-containing chemotherapy. This indication is approved under  accelerated approval based on tumor response rate and duration of response. Continued  approval for this indication may be contingent upon verification and description of clinical  benefit in confirmatory trials.   OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12  years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient  (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a  fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated  approval based on overall response rate and duration of response. Continued approval for this  indication may be contingent upon verification and description of clinical benefit in confirmatory  trials.   OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment  of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or  mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed  following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is  approved under accelerated approval based on overall response rate and duration of response.  Continued approval for this indication may be contingent upon verification and description of  clinical benefit in confirmatory trials.   OPDIVO® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma  (HCC) who have been previously treated with sorafenib. This indication is approved under  accelerated approval based on tumor response rate and durability of response. Continued  approval for this indication may be contingent upon verification and description of clinical  benefit in the confirmatory trials.   OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with  involvement of lymph nodes or metastatic disease who have undergone complete resection.  U.S. FDA-APPROVED INDICATIONS FOR YERVOY® (ipilimumab)  YERVOY® (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma  in adults and pediatric patients (12 years and older).  YERVOY® (ipilimumab) is indicated for the adjuvant treatment of patients with cutaneous  melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have  undergone complete resection, including total lymphadenectomy.  IMPORTANT SAFETY INFORMATION  WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS  YERVOY can result in severe and fatal immune-mediated adverse reactions. These  immune-mediated reactions may involve any organ system; however, the most common  severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis  (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of  these immune-mediated reactions initially manifested during treatment; however, a  minority occurred weeks to months after discontinuation of YERVOY.     

 

                                                                          Execution Version                                                                                           Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and  endocrinopathy, and evaluate clinical chemistries including liver function tests (LFTs),  adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and  before each dose.  Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy  for severe immune-mediated reactions.  Immune-Mediated Pneumonitis  OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor  patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer  corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3  or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal  cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis  occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3  mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In RCC patients  receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in  4.4% (24/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with  YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7% (2/119) of patients.  In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0%  (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9%  (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).  Immune-Mediated Colitis  OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of  colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis.  Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or  recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold  OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent  colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9%  (58/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune- mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In RCC  patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred  in 10% (52/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with  YERVOY 1 mg/kg, immune-mediated colitis occurred in 7% (8/119) of patients.  In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of  ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated  enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study  (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and  26 (5%) were hospitalized for severe enterocolitis.  Immune-Mediated Hepatitis  OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior  to and periodically during treatment. Administer corticosteroids for Grade 2 or greater  transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and  permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO  and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to  >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at  baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5  times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently  discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the  ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy,    

 

                                                                          Execution Version                                                                                           immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving  OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis occurred in 13% (51/407)  of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune- mediated hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR mCRC patients  receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 8%  (10/119) of patients.  In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in  5% (8/154) of patients receiving OPDIVO.  In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal  hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN;  Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in  0.4%.  Immune-Mediated Neuropathies  In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and  1 case of severe (Grade 3) peripheral motor neuropathy were reported.  Immune-Mediated Endocrinopathies  OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency,  autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and  symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior  to and periodically during treatment, and hyperglycemia. Administer hormone replacement as  clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2  or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for  Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade  3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism.  Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and  permanently discontinue for Grade 4 hyperglycemia.  In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of  patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypophysitis occurred  in 9% (36/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,  hypophysitis occurred in 4.6% (25/547) of patients. In MSI-H/dMMR mCRC patients receiving  OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hypophysitis occurred in 3.4%  (4/119) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred  in 1% (20/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,  adrenal insufficiency occurred in 5% (21/407) of patients. In RCC patients receiving OPDIVO 3  mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547) of patients. In MSI- H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal  insufficiency occurred in 5.9% (7/119) of patients. In patients receiving OPDIVO monotherapy,  hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients.  Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In  patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypothyroidism or thyroiditis  resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in  8% (34/407) of patients receiving this dose of OPDIVO with YERVOY. In RCC patients  receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in  hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism occurred in 12%  (66/547) of patients receiving this dose of OPDIVO with YERVOY. In MSI-H/dMMR mCRC  patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis  resulting in hypothyroidism occurred in 15% (18/119) of patients. Hyperthyroidism occurred in  12% (14/119) of patients. In patients receiving OPDIVO monotherapy, diabetes occurred in  0.9% (17/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg,    

 

                                                                          Execution Version                                                                                           diabetes occurred in 1.5% (6/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with  YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.  In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated  endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with  activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had  hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal  insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for  severe endocrinopathies.  Immune-Mediated Nephritis and Renal Dysfunction  OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine  prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased  serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4  increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated  nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving  OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated nephritis and renal dysfunction  occurred in 2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY  1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of  patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,  immune-mediated nephritis and renal dysfunction occurred in 1.7% (2/119) of patients.  Immune-Mediated Skin Adverse Reactions and Dermatitis  OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and  toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for  Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For  symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care  for assessment and treatment; if confirmed, permanently discontinue. In patients receiving  OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In  patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash occurred in  22.6% (92/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,  immune-mediated rash occurred in 16% (90/547) of patients. In MSI-H/dMMR mCRC patients  receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 14%  (17/119) of patients.  In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune- mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash  complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic  manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of  toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.  Immune-Mediated Encephalitis  OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic  symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and  lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic  signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out,  administer corticosteroids and permanently discontinue OPDIVO for immune-mediated  encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2%  (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of  exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis  occurred in one patient receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg (0.2%) after 1.7  months of exposure. Encephalitis occurred in one RCC patient receiving OPDIVO 3 mg/kg with  YERVOY 1 mg/kg (0.2%) after approximately 4 months of exposure. Encephalitis occurred in     

 

                                                                          Execution Version                                                                                           one MSI-H/dMMR mCRC patient (0.8%) receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg  after 15 days of exposure.  Other Immune-Mediated Adverse Reactions  Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO,  administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy.  Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following  clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in  <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, uveitis, iritis,  pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica,  autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory  response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis  (Kikuchi lymphadenitis), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and  myasthenic syndrome.  If uveitis occurs in combination with other immune-mediated adverse reactions, consider a  Vogt-Koyanagi-Harada-like syndrome, which has been observed in patients receiving OPDIVO  and may require treatment with systemic steroids to reduce the risk of permanent vision loss.  Infusion Reactions  OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in  clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or  slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO  monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of  patients. In a separate study in which patients received OPDIVO monotherapy as a 60-minute  infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7%  (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients,  respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay,  permanent discontinuation or withholding of OPDIVO. In patients receiving OPDIVO 1 mg/kg  with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of  patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related  reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving  OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 4.2% (5/119) of  patients.  Complications of Allogeneic Hematopoietic Stem Cell Transplantation  Fatal and other serious complications can occur in patients who receive allogeneic  hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1  receptor blocking antibody. Transplant-related complications include hyperacute graft-versus- host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after  reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified  infectious cause). These complications may occur despite intervening therapy between PD-1  blockade and allogeneic HSCT.  Follow patients closely for evidence of transplant-related complications and intervene promptly.  Consider the benefit versus risks of treatment with a PD-1 receptor blocking antibody prior to or  after an allogeneic HSCT.  Embryo-Fetal Toxicity  Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when  administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus.  Advise females of reproductive potential to use effective contraception during treatment with an     

 

                                                                          Execution Version                                                                                           OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of  OPDIVO.  Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a  Thalidomide Analogue and Dexamethasone  In clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide  analogue plus dexamethasone resulted in increased mortality. Treatment of patients with  multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide  analogue plus dexamethasone is not recommended outside of controlled clinical trials.  Lactation  It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs,  including antibodies, are excreted in human milk and because of the potential for serious  adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to  discontinue breastfeeding during treatment. Advise women to discontinue breastfeeding during  treatment with YERVOY and for 3 months following the final dose.  Serious Adverse Reactions  In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO  (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The  most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients  receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase,  and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients  receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients  receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of  patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea  (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions  leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and  Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO  plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%)  serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm,  respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and  1.0%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients  receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of  patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural  effusion, pneumonitis, and respiratory failure. In Checkmate 032, serious adverse reactions  occurred in 45% of patients receiving OPDIVO (n=245). The most frequent serious adverse  reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea,  pneumonitis, pleural effusions, and dehydration. In Checkmate 025, serious adverse reactions  occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse  reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia,  diarrhea, and hypercalcemia. In Checkmate 214, serious adverse reactions occurred in 59% of  patients receiving OPDIVO plus YERVOY and in 43% of patients receiving sunitinib. The most  frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia,  pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and  colitis; in patients treated with sunitinib, they were pneumonia, pleural effusion, and dyspnea. In  Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose  delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse  reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in  ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural  effusion, pneumonitis, and rash. Eleven patients died from causes other than disease  progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection     

 

                                                                          Execution Version                                                                                           8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In  Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO  (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving  OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.  In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO  (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving  OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general  physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving  OPDIVO with YERVOY, serious adverse reactions occurred in 47% of patients. The most  frequent serious adverse reactions reported in ≥2% of patients were colitis/diarrhea, hepatic  events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040,  serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious  adverse reactions reported in ≥2% of patients were pyrexia, ascites, back pain, general  physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4  adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent  Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea  and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO- treated patients.  Common Adverse Reactions  In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268)  was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with  OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain  (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most  common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue  (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%),  musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%),  headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and  increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse  reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain  (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract  infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia  (21%), and vomiting (20%). In Checkmate 017 and 057, the most common adverse reactions  (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough,  dyspnea, and decreased appetite. In Checkmate 032, the most common adverse reactions  (≥20%) in patients receiving OPDIVO (n=245) were fatigue (45%), decreased appetite (27%),  musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea (21%), constipation  (20%), and cough (20%). In Checkmate 025, the most common adverse reactions (≥20%)  reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs  57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs  31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%),  back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 214, the most common  adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) vs  sunitinib (n=535) were fatigue (58% vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%),  musculoskeletal pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28%  vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), decreased appetite (21% vs 29%),  dyspnea (20% vs 21%), and vomiting (20% vs 28%). In Checkmate 205 and 039, the most  common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper  respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%),  musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141,  the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough  and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most  common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue    

 

                                                                          Execution Version                                                                                           (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In  Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the most  common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%),  nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash  (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in  MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY, the most common adverse  reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain  (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite  (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (≥20%) in  patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal  pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite  (22%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO- treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%),  diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28%  vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs  15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse  reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%).  In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%)  in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus  (31%), rash (29%), and colitis (8%).  Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed  WARNING regarding immune-mediated adverse reactions for YERVOY.  Checkmate Trials and Patient Populations  Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously  untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma,  as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of  metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of  metastatic non-squamous non-small cell lung cancer; Checkmate 032–small cell lung  cancer; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously  untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039–classical  Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the  head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR  metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate  040–hepatocellular carcinoma; Checkmate 238–adjuvant treatment of melanoma.  About Bristol-Myers Squibb  Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover,  develop and deliver innovative medicines that help patients prevail over serious diseases. For  more information about Bristol-Myers Squibb, visit us at BMS.com or follow us  on LinkedIn, Twitter, YouTube, Facebook, and Instagram.  Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb  Company. In certain countries outside the U.S., due to local laws, Celgene and Juno  Therapeutics are referred to as, Celgene, a Bristol-Myers Squibb company and Juno  Therapeutics, a Bristol-Myers Squibb company.  About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration  In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers  Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except  in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the  time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’     

 

                                                                          Execution Version                                                                                           strategic collaboration agreement to jointly develop and commercialize multiple  immunotherapies – as single agents and combination regimens – for patients with cancer  in Japan, South Korea and Taiwan.  About Nektar Therapeutics  Nektar Therapeutics is a biopharmaceutical company with a robust, wholly-owned R&D pipeline  of investigational medicines in oncology, immunology and pain as well as a portfolio of  approved partnered medicines. Nektar is headquartered in San Francisco, California, with  additional operations in Huntsville, Alabama and Hyderabad, India. Further information about  the company and its drug development programs and capabilities may be found online  at http://www.nektar.com.  About Bempegaldesleukin (BEMPEG, NKTR-214)  Bempeg is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed  to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+  effector T cells and natural killer (NK) cells, without over activating the immune system. The  agent is designed to stimulate these cancer-killing immune cells in the body by targeting  CD122-specific receptors found on the surface of these immune cells. CD122, which is also  known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to  increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with  bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro- environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing  checkpoint inhibitor class of approved medicines.  Bristol-Myers Squibb Forward Looking Statements  This press release contains “forward-looking statements” within the meaning of the Private  Securities Litigation Reform Act of 1995 regarding, among other things, the research,  development and commercialization of pharmaceutical products and the collaboration  with Nektar Therapeutics. All statements that are not statements of historical facts are, or may  be deemed to be, forward-looking statements. Such forward-looking statements are based on  historical performance and current expectations and projections about our future financial  results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties,  including internal or external factors that could delay, divert or change any of them in the next  several years, that are difficult to predict, may be beyond our control and could cause our future  financial results, goals, plans and objectives to differ materially from those expressed in, or  implied by, the statements. These risks, assumptions, uncertainties and other factors include,  among others, that the expected benefits of, and opportunities related to, the collaboration  with Nektar Therapeutics may not be realized by Bristol-Myers Squibb or may take longer to  realize than anticipated and that Opdivo, in combination with bempegaldesleukin, may not  achieve their primary study endpoints or receive regulatory approval for the indications  described in this release in the currently anticipated timeline or at all and, if approved, whether  such combination treatment for such indications described in this release will be commercially  successful. No forward-looking statement can be guaranteed. Forward-looking statements in  this press release should be evaluated together with the many risks and uncertainties that  affect Bristol-Myers Squibb’s business and market, particularly those identified in the cautionary  statement and risk factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for  the year ended December 31, 2018, as updated by our subsequent Quarterly Reports on Form  10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange  Commission. The forward-looking statements included in this document are made only as of the  date of this document and except as otherwise required by applicable law, Bristol-Myers  Squibb undertakes no obligation to publicly update or revise any forward-looking statement,  whether as a result of new information, future events, changed circumstances or otherwise.     

 

                                                                             Execution Version                                                                                                 Nektar Therapeutics Cautionary Note Regarding Forward-Looking Statements     This press release contains forward-looking statements which can be identified by words such     as: "will," "move forward," "plan" and similar references to future periods. Examples of forward-    looking statements include, among others, statements we make regarding the therapeutic     potential of bempegaldesleukin ("bempeg") in combination with nivolumab, and the availability     of results and outcomes from studies of the therapies based on bempeg combinations.     Forward-looking statements are neither historical facts nor assurances of future performance.     Instead, they are based only on our current beliefs, expectations and assumptions regarding     the future of our business, future plans and strategies, anticipated events and trends, and other     future conditions. Because forward-looking statements relate to the future, they are subject to     inherent uncertainties, risks and changes in circumstances that are difficult to predict and many     of which are outside of our control. Our actual results may differ materially from those indicated     in the forward-looking statements. Therefore, you should not rely on any of these forward-    looking statements. Important factors that could cause our actual results to differ materially     from those indicated in the forward-looking statements include, among others: (i) our     statements regarding the therapeutic potential of bempeg are based on preclinical and clinical     findings and observations; (ii) bempeg is currently in clinical development and the risk of failure     remains high and failure can unexpectedly occur at any stage for one or more of the cancer     indications being studied prior to regulatory approval due to lack of sufficient efficacy, safety     considerations or other factors that impact drug development; (iii) data reported from ongoing     preclinical and clinical trials are necessarily interim data only and the final results will change     based on continuing observations; (iv) scientific discovery of new medical breakthroughs is an     inherently uncertain process and the future success of potential of bempeg is therefore very     uncertain and unpredictable; (v) the timing of the commencement or end of clinical studies and     the availability of clinical data may be delayed or unsuccessful due to regulatory delays, slower     than anticipated patient enrollment, manufacturing challenges, changing standards of care,     evolving regulatory requirements, clinical trial design, clinical outcomes, delays caused by our     collaboration partners, and enrollment competition; (vi) patents may not issue from our patent     applications for our drug candidates, patents that have issued may not be enforceable, or     additional intellectual property licenses from third parties may be required; and (vii) certain     other important risks and uncertainties set forth in Nektar's Quarterly Report on Form 10-Q filed     with the Securities and Exchange Commission on November 7, 2019. Any forward-looking     statement made by us in this press release is based only on information currently available to     us and speaks only as of the date on which it is made. We undertake no obligation to update     any forward-looking statement, whether written or oral, that may be made from time to time,     whether as a result of new information, future developments or otherwise.     References:   1.  Boyman, J., et al., Nature Reviews Immunology, 2012, 12, 180-190.   2.  Charych, D., et al., Clin Can Res; 22(3) February 1, 2016   3.  Diab, A., et al., Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1): P369                  For Bristol-Myers Squibb     Media:     media@bms.com     609-252-3345        

 

                                                                          Execution Version                                                                                           Investors:  Tim Power, 609-252-7509, timothy.power@bms.com  Nina Goworek, 908-673-9711, ngoworek@celgene.com  For Nektar  Investors:  Vivian Wu of Nektar Therapeutics  628-895-0661  Media:  Dan Budwick of 1AB  973-271-6085  dan@1abmedia.com

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