Document:

ceb-ex101_6.htm

Exhibit 10.1

TRANSITION AGREEMENT

 

THIS TRANSITION AGREEMENT (this “Agreement”) is entered into as of August 30, 2016 (the “Effective Date”) by and between CEB Inc., a Delaware corporation (the “Company”), and Thomas L. Monahan III, an individual (“Executive”).  

WHEREAS, Executive currently serves as the Chairman and Chief Executive Officer of the Company;

WHEREAS, Executive and the Company are parties to an Executive Severance Agreement dated as of February 3, 2012 (the “Severance Agreement”, of which a copy is attached as Exhibit A) and an Agreement Concerning Exclusive Services, Confidential Information, Business Opportunities, Non-Competition, Non-Solicitation, and Work Product dated as of August 20, 1997 (the “Covenants Agreement”, of which a copy is attached as Exhibit B) and an Employment Agreement dated May 16, 2001 (the “Employment Agreement”, of which a copy is attached as Exhibit C) and an Indemnity Agreement dated February 28, 2011 (the “Indemnity Agreement”, of which a copy is attached as Exhibit D);

WHEREAS, Executive has informed the Company’s board of directors (the “Board”) that he has decided to voluntarily resign all of his positions with the Company and its affiliates; 

WHEREAS, the Company and Executive (each, a “Party”) desire to set forth the terms of Executive’s voluntary resignation from the Company, to establish a transition period during which Executive shall continue to serve as an employee of the Company, and to modify the terms and conditions of Executive’s non-competition obligations under the Covenants Agreement for the benefit of the Company in exchange for reasonable payments to Executive; 

NOW, THEREFORE, in consideration of the premises, and the promises and agreements set forth below, the Parties, intending to be legally bound, agree as follows:

	
1.
	
Transition Period.  

	
 
	
(a)
	
The Parties agree that Executive shall remain an employee of the Company through June 30, 2017 (the date of this Agreement through such date, the “Transition Period”), subject to the Company’s right to earlier terminate Executive’s employment for Cause (as defined in, and determined under, the Severance Agreement) or Executive’s death or disability (as defined in the Severance Agreement) (and, in the event of any such termination, the Transition Period shall end on the date thereof).  In addition, the Company may request that Executive extend the Transition Period on a month-by-month basis, for a total of up to six months (i.e., through as late as December 31, 2017), and Executive may agree to do so in his discretion.  For the avoidance of doubt, the Company may not terminate Executive’s employment without Cause prior to June 30, 2017.

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(b)
	
Executive shall continue to serve as Chairman and Chief Executive Officer of the Company through the end of the Transition Period or, if earlier, when a new Chief Executive Officer has assumed his/her position as Chief Executive Officer (whether on an interim basis or otherwise).  Upon and following the date on which a new Chief Executive Officer has assumed his/her position as Chief Executive Officer, Executive shall remain employed with the Company for the remainder of the Transition Period, and shall perform such duties as reasonably requested by such new Chief Executive Officer and the Board.  Effective as of the end of the Transition Period, Executive hereby resigns all positions with the Company and its affiliates, including his position as a member of the Board.

	
 
	
(c)
	
Notwithstanding the Severance Agreement, in no event shall Executive be entitled to any benefits pursuant to Section 1 of the Severance Agreement that are not also provided under this Agreement, and Executive shall not be deemed to have been terminated without “cause” or to have resigned for “good reason” for purposes of any plan or agreement covering Executive.

	
2.
	
Compensation During Transition Period.  

	
 
	
(a)
	
Base Salary.  During the Transition Period, Executive shall continue to be paid his base salary at the rate in effect on the Effective Date (i.e., at the rate of $920,000 per annum), in accordance with the Company’s standard payroll procedures.

	
 
	
(b)
	
2016 Bonus.  Executive shall be entitled to a cash bonus for calendar year 2016 in an amount determined in accordance with the terms of the applicable bonus arrangement, subject to Executive’s continued employment with the Company through the date the bonus is payable (provided that, if Executive dies prior to the payment date, his estate shall be paid a prorated target bonus for 2016 based on the number of days he was employed by the Company in 2016 divided by 366), which shall be at the same time bonuses are paid to the Company’s senior executives generally. 

	
 
	
(c)
	
2017 Bonus.  Executive shall receive a cash bonus for 2017 at the “target” level (i.e., $920,000), multiplied by the greater of (x) a fraction, the numerator of which is the number of days Executive is an employee of the Company in 2017 and the denominator of which is 365 and (y) unless the Transition Period is terminated by the Company for Cause before June 30, 2017, 181/365.  Any such bonus shall be paid within thirty (30) days following the end of the Transition Period. 

	
 
	
(d)
	
Employee Benefits.  During the Transition Period, Executive shall be entitled to actively participate in the Company’s employee benefit plans (including all of the plans, programs and benefits described in Section 4 of the Employment Agreement) in accordance with applicable plan and program terms as in effect from time-to-time.  Upon the end of the Transition Period, Executive’s rights under each such plan and program shall be determined in accordance with the terms of such plans and programs as in effect from time-to-time (including, without limitation, the Company’s Retiree Medical Policy, of which a copy is 

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attached as Exhibit E).  Upon the end of the Transition Period, Executive shall also be entitled to exercise his COBRA rights.

	
 
	
(e)
	
Equity Awards.  Executive’s outstanding equity awards in the Company shall continue to vest in accordance with their terms during the Transition Period and, subject to the terms of any clawback policy of the Company in effect for senior executives, all such vested awards shall be non-forfeitable as of the end of the Transition Period.  For the avoidance of doubt, any equity awards that do not vest during the Transition Period in accordance with their terms shall be forfeited at the end of the Transition Period.  No new equity awards shall be granted to Executive during the Transition Period. 

	
 
	
(f)
	
Other Benefits.  During the Transition Period and thereafter, Executive shall be entitled to any additional or other benefits to which he is then entitled under the then-applicable terms of any applicable plan, program, agreement, or arrangement of the Company or any of its affiliates (collectively, “Company Arrangements”, and including without limitation the Severance Agreement (as modified by this Agreement), the Indemnity Agreement, and the Company’s Deferred Compensation Plan).  The Company confirms that Executive’s aggregate balance in its Deferred Compensation Plan was $13,628,001 as of August 19, 2016, and is and will remain fully vested and non-forfeitable (subject only to change in value due to contributions after August 19, 2016, and phantom investment results).  In the event of a “change in/of control” as defined in any Company Arrangement, Executive shall be entitled to any benefit to which he would have been entitled under the applicable terms and conditions of such Company Arrangement, to the extent that such benefit exceeds the corresponding benefit (if any) to which he is entitled under this Agreement. 

	
3.
	
Non-Competition and Non-Solicitation of Customers.  Sections 5(b) and 5(d) of the Covenants Agreement are deleted and replaced with “[Reserved]”; the last sentence of Section 5(e) of the Covenants Agreement is deleted; and Section 5(a) of the Covenants Agreement is amended to read as follows:

The Employee shall not, directly or indirectly, either individually or as a stockholder, director, officer, partner, consultant, owner, employee, agent, or in any other capacity, for a period of three (3) years following the end of the Transition Period, (i) manage, direct, provide or sell Company Services or work for or provide services to any person or entity that provides Company Services, within the United States or in any foreign country in which the Company or its affiliates has an office, is or has engaged in business, or proposes to engage in business as of the end of the Transition Period or (ii) induce or attempt to induce or otherwise counsel, advise, ask or encourage any person or entity who was a customer of the Company within the two (2) year period prior to the end of the Transition Period to purchase Company Services from a person or entity other than the Company or to cease or decrease the amount of such customer’s business with the Company. For the purposes of this Section 5(a), the term “Company Services” shall mean products or services that compete with those Company 

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products or services that, as of the end of the Transition Period, (i) the Company is offering or (ii) Employee knows the Company has plans to offer.  Notwithstanding the foregoing, Employee may work for or provide services to a person or entity that provides Company Services if Employee’s work or services are for a separate division of such person or entity that is wholly unrelated to the division that provides Company Services, and provided further that Employee is not involved in any way, directly or indirectly, in the management, direction, provision or sale of Company Services. 

	
4.
	
Non-Solicitation of Employees.  Section 6 of the Covenants Agreement is amended to read as follows:

The Employee agrees that during the term of his employment, and for a period of three (3) years following the end of the Transition Period, he shall not, except in the course of his duties for the Company, directly or indirectly, induce or attempt to induce or otherwise counsel, advise, ask or encourage (i) any person who at the time is a current employee of the Company or its affiliates, or who left such employ within the preceding six (6) months, to leave the employ of the Company or to accept employment or an independent contractor arrangement with another employer besides the Company, or (ii) any person or entity who at the time is a current independent contractor, consultant or vendor of the Company or its affiliates to cease or decrease the amount of such contractor’s, consultant’s or vendor’s services to the Company.   

	
5.
	
Payment for Non-Competition and Non-Competition Obligations.  In exchange for the enhanced non-competition and non-solicitation protections afforded to the Company pursuant to Sections 3 and 4 of this Agreement, the Company shall pay Executive the following amounts, subject to his continued compliance with his obligations under the Covenants Agreement (as modified by this Agreement):  (a) $750,000 on or before December 31, 2017; (b) $750,000 on or before June 30, 2018; (c) $500,000 on or before December 31, 2018; (d) $500,000 on or before June 30, 2019; (e) $250,000 on or before December 31, 2019; and (f) $250,000 on or before June 30, 2020.  Notwithstanding the foregoing, no amount shall be payable pursuant to this Section 5 if the Transition Period ends because the Company terminates Executive’s employment for Cause.  In the event that the Company fails to timely pay any of the foregoing amounts, and does not cure such failure on 15 days’ written notice from Executive to the Company requesting cure, then, if Executive so elects in writing in his sole discretion, the restrictions in Sections 3 and 4 shall be null and void and only the restrictions in the Covenants Agreement shall apply (and, for the avoidance of doubt, if the Transition Period is terminated by the Company for Cause, no amounts shall be due under this Section 5 but the restrictions referred to in Sections 3 and 4 shall continue in full force and effect).

	
6.
	
Release of Claims.  The Company and Executive shall execute the Release of Claims attached as Exhibit F on or within forty-five (45) days following the last day of the Transition Period.

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7.
	
Nondisparagement.  Executive agrees not to intentionally make, or intentionally cause any other person to make, any public statement that is intended to criticize or disparage the Company, its affiliates, or any of their respective senior executive officers or directors.  The Company agrees to use its best reasonable efforts to cause its senior executive officers and directors not to intentionally make, or intentionally cause any other person to make, any public statement that is intended to criticize or disparage Executive.  This Section 7 shall not be construed to prohibit any person from responding publicly to incorrect public statements or from making truthful statements to government authorities or when required by law, subpoena, court order, or the like.  In accordance with the Defend Trade Secrets Act, if Executive makes a confidential disclosure of a Company trade secret or other confidential information to a government official or an attorney for purposes of reporting a suspected violation of law, or in a court filing under seal, Executive shall not be held liable under this Agreement, the Covenants Agreement or any federal or state trade secret law for such a disclosure.  

	
8.
	
Cooperation.  During the Transition Period and thereafter Executive will, upon reasonable request and subject to such reasonable conditions as Executive may reasonably request: (a) cooperate with the Company in connection with any matter that arose during Executive’s employment and that relates to the business or operations of the Company or any of its parent or subsidiary corporations or affiliates, or of which Executive may have any knowledge or involvement; and (b) consult with and provide information to the Company and its representatives concerning such matters.  If any such cooperation is required after the Transition Period, such cooperation shall be required only at reasonable times and places and in a manner that does not unreasonably interfere with any other employment in which Executive may then be engaged.  Nothing in this Agreement shall be construed or interpreted as requiring Executive to provide any testimony or affidavit that is not truthful.

	
9.
	
Indemnification.  The Company shall maintain, for the benefit of Executive, director and officer liability insurance in a form at least as comprehensive as, and in an amount that is at least equal to, that maintained by the Company for any other officer or director.  In addition, Executive shall be indemnified by the Company against liability for claims against him as an officer and director of the Company and shall be entitled to prompt advancement of expenses (including without limitation attorney’s fees), in each case to the fullest extent provided in the Indemnity Agreement, Section 15 of the Severance Agreement, the Company’s bylaws and/or any other governing documents applicable to Executive, whichever is most favorable to Executive in the particular instance.  Executive’s rights under this Section 9 shall continue so long as he may be subject to such liability.

	
10.
	
Withholdings.  Amounts payable hereunder are subject to all tax and other legally-required withholdings.

	
11.
	
Queries Regarding Covenants.  Any questions Executive has regarding the application of his obligations under the Covenants Agreement (as amended hereby) shall be directed to the Lead Director or Non-Executive Chairman of the Board.

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12.
	
No Assignment.  No right to receive payments and benefits under this Agreement shall be subject to set off, offset, anticipation, commutation, alienation, assignment, encumbrance, charge, pledge or hypothecation or to execution, attachment, levy, or similar process or assignment by operation of law, except as provided in this Agreement.

	
13.
	
Entire Agreement.  This Agreement, together with the Severance Agreement and the Covenants Agreement (each as modified hereby), represents the entire understanding and agreement between the parties as to the subject matter hereof and supersedes all prior agreements, arrangements and understandings between them concerning the subject matter hereof, and any subsequent written agreements shall be construed to change, amend, alter, repeal or invalidate this Agreement, only to the extent that this Agreement is specifically identified in and made subject to such other written agreements and is executed by both parties hereto.  For the avoidance of doubt, the Covenants Agreement and the Severance Agreement shall remain in full force and effect in accordance with their terms, except as modified by this Agreement.  

	
14.
	
Governing Law.  This Agreement and its performance, together with the Severance Agreement and the Covenants Agreement (each as modified hereby) and their performance, will be construed and interpreted in accordance with the laws of the State of Delaware, without regard to principles of conflicts of law that would apply the substantive law of any other jurisdiction.  Notwithstanding anything in this Agreement or elsewhere to the contrary, the parties agree irrevocably to submit to the exclusive jurisdiction of the federal courts or, if no federal jurisdiction exists, the state courts, located in the State of Delaware, for the purposes of any suit, action or other proceeding arising out of or relating to Executive’s employment with the Company, the termination of such employment, or rights arising under or preserved by this Agreement, and hereby waive, and agree not to assert by way of motion, as a defense or otherwise, in any such suit, action, or proceeding, any claim that it is not personally subject to the jurisdiction of the above-named courts, that the suit, action or proceeding is brought in an inconvenient forum, that the venue of the suit, action or proceeding is improper, or that the provisions of this Agreement may not be enforced in or by such courts; provided, however, that Section 5(c) of the Severance Agreement shall apply to any such proceeding as if it were an arbitration.  IN ADDITION, EACH PARTY WAIVES ANY RIGHT TO TRIAL BY JURY OF ANY CLAIM ARISING OUT OF THE EMPLOYMENT RELATIONSHIP BETWEEN THE PARTIES, INCLUDING, BUT NOT LIMITED TO, ISSUES ARISING OUT OF THIS AGREEMENT.

	
15.
	
Interpretation.  Whenever possible, each provision of this Agreement shall be interpreted in such manner as to be effective and valid under applicable law, but if any provision of this Agreement is held to be invalid, illegal or unenforceable in any respect under any applicable law or rule in any jurisdiction, such invalidity, illegality or unenforceability shall not affect any other provision or any other jurisdiction, but this Agreement shall be reformed, construed and enforced in such jurisdiction as if such invalid, illegal or unenforceable provision had never been contained herein.

	
16.
	
Miscellaneous.  In the event of Executive’s death or a judicial determination of his incompetence, references to Executive in this Agreement and in the Release shall (where 

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appropriate) be deemed to refer to his heir(s), beneficiar(ies), estate, executor(s) or other legal representative(s).  Notwithstanding anything in this Agreement or elsewhere to the contrary, Executive shall at all times be entitled to: (i) retain, and use appropriately, (x) documents and information relating to his personal entitlements and obligations, and (y) his rolodex (and electronic equivalents); (ii) disclose documents and information in confidence to an attorney or other professional for the purpose of securing professional advice; and (iii) make truthful statements, and disclose documents and information, (w) when required by law, subpoena, court order or the like, (x) when requested by or voluntarily disclosed to a governmental or self-regulatory authority, (y) when protected by applicable “whistleblower” statutes, or (z) as reasonably necessary to enforce his rights in a proceeding under Section 14 or otherwise.

 

	
DATE:  August 30, 2016
	
/s/ Thomas L. Monahan III
Thomas L. Monahan III

 

/s/ Melody Jones
For CEB Inc. 

 

7Exhibit
10.3

Amendment #2

 

Cooperative Research and Development Agreement
# 02734

 

“Cooperative Research and Development Agreement
for the Development and Evaluation of the NCI Proprietary Adoptive Cell Transfer Immunotherapy Using Tumor-Infiltrating Lymphocytes
in Patients with Metastatic Melanoma, Bladder, Lung, Breast, and HPV-associated Cancers, Utilizing Lion Biotechnologies, Inc.’s
Business Development Expertise in Adoptive Cell Transfer Immunotherapy”

 

The purpose of this amendment is to change certain terms
of the above-referenced Cooperative Research and Development Agreement (CRADA). These changes are reflected below, and except for
these changes and those of Amendments #1, all other provisions of the original CRADA remain in full force and effect. Two originals
of this amendment are provided for execution; one is to remain with the National Cancer Institute and the other is to remain with
the Collaborator.

 

1)Upon final signature,
the term of the CRADA is extended for five (5) years from August 05, 2016 to August 05, 2021. 

 

2)Title of the CRADA
is modified to “Cooperative Research and Development Agreement for the Development and Evaluation of the NCI Proprietary
Adoptive Cell Transfer Immunotherapy Using Unmodified Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma, Bladder,
Lung, Breast, and HPV-associated Cancers, Utilizing Lion Biotechnologies, Inc.’s Business Development Expertise in Adoptive
Cell Transfer Immunotherapy”.

 

3)Chief Executive
Officer of Lion Biotechnologies Inc. is changed from Dr. Elma Hawkins, to Dr. Maria Fardis, effective June 1st, 2016.

 

4)Address of Lion
is changed to: 112 West 34 Street, 18th Floor, New York, NY 10120

 

5)Appendix A –
Goals of the CRADA is amended to exclude modified or genetically altered TIL. The goals of the CRADA are limited to development
of unmodified TIL as a stand-alone therapy or in combination with FDA licensed products and commercially available reagents routinely
used for ACT therapy. Modified Appendix A is included as Addendum-1. 

 

	PHS ICT-CRADA	CRADA Ref. No. 02734	MODEL ADOPTED June 18, 2009 
	Page 1 of 12	 	Confidential

     

     

    

  

6) Appendix A-Goals
of the CRADA is amended to allow Dr. Rosenberg to collaborate with third parties on projects designed at improving TIL that are
outside the scope of this CRADA. 

 

7)Appendix B- Staffing,
Funding and Materials/Equipment Contributions of the Parties is amended to reflect Material contributions and payment options.
Modified Appendix B is included as Addendum-2.

 

SIGNATURES BEGIN ON THE NEXT
PAGE

 

	PHS ICT-CRADA	CRADA Ref. No. 02734	MODEL ADOPTED June 18, 2009 
	Page 2 of 12	 	Confidential

 

     

     

    

  

	Accepted and Agreed to: 	 	 
	 	 	 
	For the National Cancer Institute: 	 	 
	 	 	 
	/s/ JAMES DOROSHOW, M.D.	 	 	8/18/16
	 	 	 
	James Doroshow, M.D.	 	Date
	 	 	 
	Deputy Director for Clinical and Translational Research, NCI	 	 
	 	 	 
	For the Collaborator: 	 	 
	 	 	 
	/s/ MARIA FARDIS, PH.D.	 	 	8/18/16
	Maria Fardis, Ph.D.	 	Date
	President and Chief Executive Officer	 	 
	Lion Biotechnologies, Inc.	 	 

 

	PHS ICT-CRADA	CRADA Ref. No. 02734	MODEL ADOPTED June 18, 2009 
	Page 3 of 12	 	Confidential

 

     

     

    

  

ADDENDUM-1 TO AMENDMENT -2 

 

PUBLIC HEALTH SERVICE

COOPERATIVE RESEARCH AND DEVELOPMENT
AGREEMENT

FOR INTRAMURAL-PHS CLINICAL RESEARCH

 

APPENDIX A

 

RESEARCH PLAN

 

Title of CRADA

Cooperative Research and Development Agreement
for the Development and Evaluation of the NCI Proprietary Adoptive Cell Transfer Immunotherapy Using Unmodified Tumor-Infiltrating
Lymphocytes in Patients with Metastatic Melanoma, Bladder, Lung, Breast, and HPV-associated Cancers, Utilizing Lion Biotechnologies,
Inc.’s Business Development Expertise in Adoptive Cell Transfer Immunotherapy

 

 

NCI Principal Investigator

Steven A. Rosenberg, M.D., Ph.D.

Chief, Surgery Branch

Center for Cancer Research (CCR)

National Cancer Institute (NCI)

 

Collaborator Principal Investigator

Maria Fardis, Ph.D., M.B.A.

Chief Executive Officer

Lion Biotechnologies, Inc.

 

Term of CRADA

Ten (10) years from the date of the final
CRADA signature.

_____________________________________________________________________________

 

Goals
of this CRADA

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4 of 12

     

     

    

  

The principal goal of this CRADA is to develop and evaluate
effective adoptive cell transfer-based immunotherapies (ACT) using unmodified Tumor-Infiltrating Lymphocytes (TIL), where the ACT/TIL
therapy approach is proprietary to the NCI, for the treatment of patients with metastatic melanoma, bladder, lung, breast, and
HPV (Human Papilloma Virus)-associated cancers, utilizing the business development expertise and resources of Lion Biotechnologies,
Inc., Specifically this CRADA will (1) support the in vitro development of improved methods for the large scale generation
and selection of unmodified TIL with anti-tumor reactivity from patients with metastatic melanoma, bladder, lung, breast, and HPV-associated
cancers, based on ACT therapies developed by and proprietary to the NCI Surgery Branch, to be used for large scale production of
TIL for the ACT treatment of patients with these cancers; (2) develop these approaches for large scale TIL generation that are
in accord with Good Manufacturing Practice (GMP) procedures suitable for use in treating patients with metastatic melanoma, bladder,
lung, breast, and HPV-associated cancers; and (3) develop clinical trials using these improved methods of large scale TIL generation
as well as improved patient preparative regimens with the goal of commercializing the ACT/TIL therapy approach for treating patients
with metastatic melanoma, bladder, lung, breast, and HPV-associated cancers. The scope of this CRADA, including any in vitro
and in vivo testing conducted by Dr. Steven A. Rosenberg and members of the NCI Surgery Branch within the CCR is strictly
limited to the development of unmodified TIL which have not been genetically altered as a single agent therapy or in combination
with FDA licensed products, and commercially available reagents routinely used for ACT therapy, such as chemotherapeutic agents,
pembrolizumab, nivolumab, ipilimumab, and aldesleukin [IL-2], in treating patients with metastatic melanoma, bladder, lung, breast,
and HPV-associated cancers, utilizing Lion’s expertise in the large scale production of adoptive cell transfer immunotherapies.
The scope of this CRADA is limited to unmodified TIL as stand-alone therapy, and shall exclude the combination of TIL with other
investigational agents, including, but not limited to, anti-cancer antibodies, as well as other investigational agents used in
cancer treatment, compounds, small molecule inhibitors, T-cell activators, cytokines, experimental therapies or others. Genetically
modified TIL, such as with various gene knockout, knockdown, or knock-in techniques, are specifically excluded from the scope of
this CRADA. If Collaborator acquires proprietary gene editing technology, the Parties may discuss at that point whether CRADA will
be amended to include such technology. Additional research or clinical activities involving current or prospective NCI Surgery
Branch adoptive immunotherapy protocols, to which Lion is not a party, are outside the scope of this CRADA unless and until the
Parties mutually agree to such studies which shall be added by written amendment to this CRADA. Dr. Rosenberg may engage in collaborations
with third parties on projects designed to explore the improvement of TIL that are outside the scope of this CRADA. Such collaborations
may involve the use of third party proprietary materials and technology and will be documented by NCI and any third party with
a duly executed agreement. Collaborator acknowledges that this may occur and unless those projects are added to this CRADA by an
amendment, the research to be conducted under these collaborations will not be included in this CRADA. NCI will be under no obligation
to share any data generated from such third party collaborations with Collaborator.

 

Expertise of the Parties

 

Dr. Steven A. Rosenberg has extensive experience in the development
and application of his proprietary adoptive cell-based therapies for patients with cancer. His laboratory has developed in vitro
techniques for generating anti-tumor T cells obtained from patient tumors under conditions suitable for subsequent infusion. Dr.
Rosenberg and his colleagues in the NCI Surgery Branch have extensive experience in the development of cell-based reagents and
the conduct of clinical trials utilizing these cells in immunotherapeutic protocols.

 

Lion Biotechnologies, Inc. has assembled a team of senior level
scientists and clinicians who have experience in the application of cell-based immunotherapies to help guide the commercial development
of ACT therapy for the treatment of metastatic melanoma, bladder, lung, breast, and HPV-associated cancers, as specified in “Goals
of this CRADA” (“Goals”) based on the NCI Surgery Branch proprietary technologies for TIL preparation and administration
of ACT to patients. Lion has contracted with GMP manufacturers to perform this work emphasizing the development and evaluation
of improved techniques for TIL generation that meet GMP standards as well as to conduct clinical trials of ACT/TIL therapy designed
to meet the standards of the FDA to achieve approval for the commercialization of this treatment approach. Thus the combination
of the scientific and clinical expertise of the NCI Surgery Branch with the scientific and clinical expertise of Lion as well as
the availability of Lion-contracted GMP production facilities to make ACT/TIL product for Lion-sponsored licensing trials represents
an ideal opportunity that can lead to the commercialization of the ACT/TIL treatment approach for patients with those cancers as
specified in “Goals”, making these treatments more widely available to patients in need.

 

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The NCI Surgery Branch and Lion thus have complementary expertise
that can develop technologies and clinical treatment approaches that have the potential to improve cell transfer therapy and make
it more widely available to patients through commercialization by Lion.

 

Experimental Plan

 

The experimental details that follow are approximate and may
be changed upon mutual agreement of the NCI and Collaborator. Any change in the scope of this CRADA will be by mutual consent and
written Amendment to the CRADA. 

 

		I.	Develop improved methods for the generation and selection of unmodified TIL with anti-tumor reactivity from patients with
metastatic melanoma, bladder, lung, breast, and HPV-associated cancers, as specified in “Goals”, based on ACT
proprietary to and developed by the NCI Surgery Branch, for use in the large-scale production of unmodified TIL for this ACT treatment
of these cancers

 

Simplified and better methods for TIL selection and
growth are needed to supplement current NCI Surgery Branch efforts in order to expand ACT/TIL therapy to a greater numbers of patients
with those cancers as specified in “Goals”. Studies of improved methods for TIL selection will be investigated by the
NCI Surgery Branch and Lion. This will include use of in vitro assays of specificity that are based on specific blocking
of Class I MHC (Major Histocompatibility Complex) molecules that can provide evidence for the specific recognition of autologous
tumor and use of sensitive assays of the upregulation of molecules such as 4-1-BB, PD-1, and/or others on the lymphocyte cell surface.
Such studies in the NCI Surgery Branch may also include the separation of phenotypically different lymphocyte subsets present in
TIL such as central memory, effector memory and terminally differentiated effector cells. NCI Surgery Branch studies in mice have
shown that lymphocyte subsets such as central memory cells can be more effective in the adoptive immunotherapy of experimental
tumors and this needs to be studied in humans with those cancers as specified in “Goals”. Other studies may include
identifying lymphocytes from an inflamed vs. non-inflamed tumor microenvironment, as inflamed tumors tend to respond better to
cancer immunotherapies.

 

In addition, NCI Surgery Branch may send fresh melanoma,
bladder, lung, breast, and HPV-associated cancer specimens from NCI protocol 03-C-0277 entitled “Cell Harvest and Preparation
for Surgery Branch Adoptive Cell Therapy Protocols” to Lion or its agents to develop techniques for growing TIL and for performing
assays involving criteria which are designed to improve TIL selection. Assays will be performed on the growing TIL to evaluate
their recognition of autologous tumor cells assessed by gamma interferon release in overnight co-culture with tumor and to evaluate
the phenotypic expression of cell surface markers on TIL such as CD62L, CD45RO, CD45RA and CD127. Such studies would form the basis
for TIL selection and generation for use in the large scale production of TIL for the treatment of patients with those cancers
as specified in “Goals”. For the avoidance of doubt, TIL shall mean genetically unmodified TIL.

 

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		II.	Develop approaches to large scale unmodified TIL generation that are in accord with Good Manufacturing Practice (GMP) procedures
suitable for their use in treating patients with metastatic melanoma, bladder, lung, breast, and HPV-associated cancers, as specified
in “Goals”

 

The selection and growth of autologous TIL from patients
with those cancers as specified in “Goals” is a vital part of the successful use of this approach. Prior NCI Surgery
Branch methods for TIL growth involved extensive in vitro testing using multiple cell lines and fresh tissue samples. Under
this CRADA, studies will be conducted to improve methods for the generation of the large numbers of unmodified TIL necessary for
patient treatment. These studies will explore the use of commercially available reagents including but not limited to cytokines,
such as IL-7, IL-15, IL-21, as well as agonist/antagonist antibodies, that can promote TIL growth. The NCI Surgery Branch has begun
some of these studies, but extensive additional studies are required to optimize cell growth including the determination of the
best concentrations of reagents, and timing of media change. These studies will be conducted by the NCI Surgery Branch with advice,
input, and expertise provided by Lion.

 

In addition, the NCI Surgery Branch may send tumor
samples from those cancers as specified in “Goals” which were collected from NCI protocol 03-C-0277 to Lion or its
agents for studies including scale-out for the methods of expansion of individualized lymphocyte treatments, assays for product
and in-process performance, and harmonization assays for centralized process development and determination of TIL product consistency.

 

Additionally, biological reagents and materials may
be sent to Lion or its agents for the development of qualifying assays and process development related to scale-out of the unmodified
TIL expansion process. Techniques thus described will need to be adapted to meet the GMP requirements of the Food and Drug Administration
for infusion into patients. This may require modification of the procedures developed in the NCI Surgery Branch. Lion and the NCI
Surgery Branch will work together to develop Standard Operating Procedures (SOP) for large scale TIL growth, selection and testing
that meet the approval of the FDA. Joint meetings with the FDA will be required to define the exact format and criteria need to
meet FDA approval.

 

		III.	Develop clinical trials using these improved methods of large-scale, unmodified TIL generation as well as improved patient
preparative regimens to treat patients with metastatic melanoma, bladder, lung, breast, and HPV-associated cancers, as specified
in “Goals”

 

Clinical trials will be designed and implemented to
evaluate the clinical effectiveness of ACT/TIL therapy resulting from large scale techniques in patients with those cancers as
specified in “Goals”, based on the proprietary NCI Surgery Branch technology and approaches developed in the first
two parts of the Experimental Plan. Lion and the NCI Surgery Branch will work together to develop multi-institutional clinical
trials evaluating the clinical effectiveness of the administration of autologous unmodified TIL generated using Lion technology
to patients with those cancers as specified in “Goals” that can potentially be used as licensing trials for FDA approval.
The NCI Surgery Branch does not have a suitable GMP facility that will meet FDA standards for the conduct of such a trial. Exploratory
pilot trials may be necessary prior to beginning a licensing trial and these may be conducted in the Surgery Branch alone or in
conjunction with other multicenter sites associated with Lion. The development and conduct of licensing trials will require the
GMP expertise of Lion and the extensive experience of the NCI Surgery Branch working together. TIL for these licensing trials to
be sponsored by Lion will be produced on a large scale at one or more central GMP facilities contracted by Lion. An IND with the
FDA will be filed by Lion which will serve as the Coordinating Center for such trials. The goal of such trials will be to generate
data to support the approval by the FDA of this ACT/TIL therapy approach. In vitro testing of patient samples from such
trials will evaluate the activity and persistence level of the transferred cells in the circulation of treated patients and will
be conducted by the NCI Surgery Branch both for any pilot trials that are performed as well as for the large multi-institutional
trials that are planned.

 

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Clinical trials may include but are not limited to
the evaluation of the addition of an FDA-approved anti-PD-1 checkpoint antibody to unmodified TIL therapy. Exploratory pilot trials
may include but are not limited to the evaluation of: 1) TIL cryopreserved prior to shipping from a central facility to patients
and 2) TIL selected for upregulated expression of PD-1 on the cell surface.

 

Description of the
Contributions and Responsibilities of the Parties

 

Surgery Branch, NCI

 

		-	Develop and test new improved and simplified in vitro methods for the selection and growth of unmodified TIL with anti-tumor
activity for large scale preparations that can be used in clinical cell transfer studies. As described in the Experimental Plan
above, this will include evaluation of new growth techniques culture vessels, and tests.

 

		-	Perform in vitro studies of the immunologic parameters surrounding the new cell transfer clinical protocol(s) by analyzing
the phenotypic and functional properties of the transferred cells and their persistence in the patient following adoptive transfer
in all clinical trials conducted under this CRADA, as outlined in Section III above.

 

		-	Support requests from Lion to provide data from studies conducted at NCI in support of regulatory submissions. Assist Lion
by reviewing the data together and addressing possible queries to the data to assure readiness of the data for health authority
submissions. Allow the data to be monitored as needed in support of health authority submissions.

 

Lion

 

		-	Develop, implement, and evaluate GMP procedures for the large-scale production of unmodified TIL suitable for infusion
into patients with metastatic melanoma, bladder, lung, breast, and HPV-associated cancers as specified in “Goals”.

 

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		-	Conduct studies including scale-out for the methods of expansion of individualized lymphocyte treatments, assays for product
and in-process performance, and harmonization assays for centralized process development and determination of TIL product consistency.
Additional studies may be conducted for the development of qualifying assays and process development related to scale-out of the
TIL expansion process.

 

		-	Consult with the FDA to determine the appropriate clinical trial design necessary to secure approval for the commercial development
of unmodified TIL therapy for patients with those cancers as specified in “Goals” and sponsor the IND for these new
clinical protocols. Serve as the coordinating center for the multicenter licensing clinical trials.

 

		-	Supply TIL in sufficient quantities to complete the planned clinical trials sponsored by Lion (including the licensing trial)
needed for FDA approval of unmodified ACT/TIL therapy

 

Surgery Branch, NCI and Lion

 

		-	Develop SOP for large scale TIL growth, selection and testing to support the FDA approval of unmodified ACT/TIL therapy. Attend
joint meetings with the FDA to define the exact format and criteria needed in the clinical trial(s) to obtain FDA approval.

 

Develop, conduct and evaluate multi-institutional clinical
trials (to include the NCI Surgery Branch as a clinical trial site) for patients with metastatic melanoma, bladder, lung, breast,
and HPV-associated cancers (as specified in “Goals”) treated with unmodified TIL that can be used as licensing trials
required for FDA approval and subsequent commercialization of unmodified ACT/TIL therapy.

 

		-	Conduct assays to be used in the selection of appropriate cells (based on both functional and phenotypic criteria) to optimize
the effectiveness of the adoptive transfer. 

 

		-	Exchange information and expertise to further the successful development of unmodified TIL therapy for patients with those
cancers as specified in “Goals”. For the avoidance of doubt, exchanging information includes but is not limited to
the transfer of preclinical and clinical data. In addition, both Parties shall meet or conduct conference calls on a regular basis
(no less than once a month) to exchange information and provide updates on the progress of the research and clinical development
as described in the Experimental Plan.

 

Related NCI and Collaborator
Agreements: None

 

Related Intellectual
Property and Business/Scientific Expertise of the Parties

 

NCI Surgery Branch

 

1) PCT/US03/27873 entitled “Immunotherapy with
In Vitro-Selected Antigen-specific Lymphocytes After Nonmyeloablative Lymphodepleting Chemotherapy,” filed 9/5/03.
Inventors: Mark E. Dudley, Steven A. Rosenberg, John R. Wunderlich. This is inclusive of all U.S. continuing applications and divisionals,
and foreign applications.

 

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2) USSN 12/869,390 entitled “Adoptive Cell Therapy
with Young T Cells”, filed 8/26/10. Inventors: Mark E. Dudley and Steven A. Rosenberg. This is inclusive of all U.S. continuing
applications and divisionals.

 

3)  PCT/US12/02974
entitled “Methods of Growing Tumor Infiltrating Lymphocytes in Gas-Permeable Containers”, filed 3/20/12. Inventors:
Steven A. Rosenberg, Mark E. Dudley, et al. This is inclusive of all U.S. continuing applications, divisionals, and foreign applications.

 

4) PCT/US14/046478 entitled “Methods of Preparing
Anti-Human Papillomavirus Antigen T Cells”, filed 7/14/2014. Inventors: Christian S. Hinrichs and Steven A. Rosenberg. This
is inclusive of all U.S. continuing applications and divisionals.

 

Lion Biotechnologies, Inc.

 

Lion has the following active licenses for NCI-owned intellectual
property: L-107-2015/1, L-108-2015/0,

 

Lion is a publicly traded biotechnology company developing therapies
for the treatment of cancer. Lion’s lead therapeutic candidate will be an autologous cell therapy product using TIL for the
treatment of metastatic melanoma. Lion may also develop TIL products for bladder, lung, breast, and HPV-associated cancers as specified
in “Goals” to be developed under this CRADA.

 

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ADDENDUM-2 TO AMENDMENT -2 

 

PUBLIC HEALTH SERVICE

COOPERATIVE RESEARCH AND DEVELOPMENT
AGREEMENT

FOR INTRAMURAL-PHS CLINICAL RESEARCH

 

APPENDIX B

 

STAFFING, FUNDING AND MATERIALS/EQUIPMENT CONTRIBUTIONS

OF THE PARTIES

 

Staffing Contributions:

 

IC will provide scientific staff and other support necessary
to conduct the research and other activities described in the Research Plan. IC’s scientific staff will include IC’s
CRADA Principal Investigator and technical staff.

 

IC estimates that 3-5 person-years of effort per year will be
required to complete the CRADA research.

 

Collaborator will provide scientific staff and other support
necessary to conduct the research and other activities described in the Research Plan. Collaborator’s scientific staff will
include Collaborator’s Principal Investigator and technical staff.

 

Collaborator estimates that 3-5 person-years of effort per year
will be required to complete the CRADA research.

 

Funding Contributions:

 

Collaborator agrees to provide funds in the amount of $2,000,000.00
per year of the CRADA for IC to use to acquire technical, statistical, and administrative support for the research activities,
as well as to pay for supplies and travel expenses. Collaborator will provide funds in the amount of $500,000.00 on a quarterly
basis. Each subsequent installment will be due within thirty (30) days of each quarterly anniversary of the CRADA Effective Date.
Collaborator agrees that IC can allocate the funding between the various categories in support of the CRADA research as IC’s
CRADA PI sees fit. For avoidance of doubt, the funding will only be used to support the research and development outlined in the
CRADA.

 

CRADA PAYMENTS:

 

Collaborator has three options for making CRADA payments. See
CRADA Payment Options at http://ttc.nci.nih.gov/forms/crada.php for specific information on making payments using each option.

 

Option 1: Collaborator sends checks to the NCI.

Option 2: Collaborator makes payments via wire transfer (Fedwire).

Option 3: Collaborator makes ACH/EFT payments using www.pay.gov.

 

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If Collaborator chooses to pay by check, the check is payable
to the National Cancer Institute and will reference the CRADA number 02734 and title “CRADA for the Development and Evaluation
of the NCI Proprietary Adoptive Cell Transfer Immunotherapy Using Unmodifed Tumor-Infiltrating Lymphocytes in Patients with Metastatic
Melanoma, Bladder, Lung, Breast and HPV-associated Cancers Utilizing Lion Biotechnologies, Inc.’s Business Development Expertise
in Adoptive Cell Transfer Immunotherapy” on each check, and will send them via trackable mail or courier to:

 

CRADA Funds Coordinator

Technology Transfer Center, NCI

9609 Medical Center Drive, Rm 1-E530, Rockville,
MD 20850-9702

 

CRADA Travel Payments:

Travel arrangements for all Government staff will be made in
accordance with the Federal Travel Rules and Regulations, whether arranged by IC and funded using either appropriated funds or
CRADA funds, or arranged and funded directly by Collaborator.

 

Materials/Equipment Contributions:

 

IC will provide the following IC Materials for use under this
CRADA:

 

	Test Article:	None
	 	 
	IC Materials:	Fresh melanoma, bladder cancer, lung cancer, triple-negative breast cancer, and HPV-associated cancer tumor specimens collected under NCI protocol 03-C-0277 entitled “Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols”
	 	 
	Capital Equipment:	None

 

If either Party decides to provide additional Materials for
use under this CRADA, those materials will be transferred under a cover letter that identifies them and states that they are being
provided under the terms of the CRADA.

 

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