Document:

Exhibit
10.21

 

LOCK-UP
AGREEMENT

 

March
2, 2022

 

Each
Purchaser referenced below:

 

		Re:	Securities
                                            Purchase Agreement, dated as of March 2, 2022 (the “Purchase Agreement”),
                                            between Curative Biotechnology, Inc., a Florida corporation (the “Company”),
                                            and the purchaser signatory thereto (the “Purchaser”)

 

Ladies
and Gentlemen:

 

Defined
terms not otherwise defined in this letter agreement (the “Letter Agreement”) shall have the meanings set forth in
the Purchase Agreement. Pursuant to the Purchase Agreement and in satisfaction of a condition of the Company’s obligations under
the Purchase Agreement, the undersigned irrevocably agrees with the Company that, from the date hereof until the earlier of (i) the Maturity
Date of the Notes issued pursuant to the Purchase Agreement or (ii) 6 months from the date of a Qualified Offering (such period, the
“Restriction Period”), the undersigned will not offer, sell, contract to sell, hypothecate, pledge or otherwise dispose
of (or enter into any transaction which is designed to, or might reasonably be expected to, result in the disposition (whether by actual
disposition or effective economic disposition due to cash settlement or otherwise) by the undersigned or any Affiliate of the undersigned
or any person in privity with the undersigned or any Affiliate of the undersigned), directly or indirectly, including sales pursuant
to a registration statement, or establish or increase a put equivalent position or liquidate or decrease a call equivalent position within
the meaning of Section 16 of the Exchange Act with respect to, any shares of common stock or common stock equivalents of the Company
beneficially owned, held or hereafter acquired by the undersigned (the “Securities”); provided however
that such restrictions will not apply to: (i) transfers of Securities as bona fide charitable contributions, gifts or donations, (ii)
transfers or dispositions of the Securities to any trust for the direct or indirect benefit of the undersigned or the immediate family
of the undersigned, (iii) transfers or dispositions of the Securities by will, other testamentary document or intestate succession to
the legal representative, heir, beneficiary or a member of the immediate family of the undersigned, (iv) transfers of the Securities
to stockholders, direct or indirect affiliates (within the meaning set forth in Rule 405 under the Securities Act), current or former
partners (general or limited), members or managers of the undersigned, as applicable, or to the estates of any such stockholders, affiliates,
partners, members or managers, or to another corporation, partnership, limited liability company or other business entity that controls,
is controlled by or is under common control with the undersigned, (v) transfers that occur by operation of law pursuant to a qualified
domestic relations order or in connection with a divorce settlement, (vi) transfers or dispositions not involving a change in beneficial
ownership, (vii) if the undersigned is a trust, transfers or dispositions to any beneficiary of the undersigned or the estate of any
such beneficiary; provided that, in each case (i) through (vii) above, the transferee agrees in writing to be bound by the terms and
conditions of this letter agreement and either the undersigned or the transferee provides Purchaser with a copy of such agreement promptly
upon consummation of any such transfer, (viii) transfers pursuant to a bona fide third party tender offer, merger, consolidation or other
similar transaction made to all holders of the Company’s capital stock involving a change of control of the Company, provided that
in the event that such tender offer, merger, consolidation or other such transaction is not completed, the Securities shall remain subject
to the restrictions contained in this Letter Agreement or (ix) the undersigned approving and assisting in the preparation of a registration
statement on Form S-8 registering the shares of Common Stock subject to the Company’s equity compensation plans, but not selling
such shares. For purposes of this Letter Agreement, “immediate family” shall mean any relationship by blood, marriage or
adoption, not more remote than first cousin.

 

    	 

     

    

 

Notwithstanding
the restrictions imposed by this Letter Agreement, the undersigned may (a) exercise an option or warrant (including a net or cashless
exercise of such option or warrant) to purchase shares of the Company’s Common Stock, provided that any such shares shall continue
to be subject to the restrictions on transfer set forth in this letter agreement, (b) Securities to cover tax withholding obligations
of the undersigned in connection with any option exercise or the vesting of any restricted stock or restricted stock unit award, provided
that any such shares shall continue to be subject to the restrictions on transfer set forth in this letter agreement, or (c) establish
a trading plan pursuant to Rule 10b5-1 under the Exchange Act for the transfer of the Securities, provided that such plan does not provide
for any transfers of Securities during the Restricted Period and provided further, that, no filing under the Exchange Act or other public
announcement shall be required or shall be made voluntarily in connection with the establishment of such a plan.

 

The
undersigned acknowledges that the execution, delivery and performance of this Letter Agreement is a material inducement to the Purchaser
to complete the transactions contemplated by the Purchase Agreement and that the Purchaser (which shall be a third party beneficiary
of this Letter Agreement), the Company shall be entitled to specific performance of the undersigned’s obligations hereunder. The
undersigned hereby represents that the undersigned has the power and authority to execute, deliver and perform this Letter Agreement,
that the undersigned has received adequate consideration therefor and that the undersigned will indirectly benefit from the closing of
the transactions contemplated by the Purchase Agreement.

 

This
Letter Agreement may not be amended or otherwise modified in any respect without the written consent of each of the Company, the Purchaser
and the undersigned. This Letter Agreement shall be construed and enforced in accordance with the laws of the State of New York without
regard to the principles of conflict of laws. The undersigned hereby irrevocably submits to the exclusive jurisdiction of the United
States District Court sitting in the Southern District of New York and the courts of the State of New York located in Manhattan, for
the purposes of any suit, action or proceeding arising out of or relating to this Letter Agreement, and hereby waives, and agrees not
to assert in any such suit, action or proceeding, any claim that (i) it is not personally subject to the jurisdiction of such court,
(ii) the suit, action or proceeding is brought in an inconvenient forum, or (iii) the venue of the suit, action or proceeding is improper.
The undersigned hereby irrevocably waives personal service of process and consents to process being served in any such suit, action or
proceeding by receiving a copy thereof sent to the Company at the address in effect for notices to it under the Purchase Agreement and
agrees that such service shall constitute good and sufficient service of process and notice thereof. The undersigned hereby waives any
right to a trial by jury. Nothing contained herein shall be deemed to limit in any way any right to serve process in any manner permitted
by law. The undersigned agrees and understands that this Letter Agreement does not intend to create any relationship between the undersigned
Purchaser and that Purchaser is not entitled to cast any votes on the matters herein contemplated and that no issuance or sale of the
Securities is created or intended by virtue of this Letter Agreement.

 

[Signature
page follows.]

 

    	-2-

     

    

 

This
Letter Agreement may be executed in two or more counterparts, all of which when taken together may be considered one and the same agreement.

 

		 	 
	Signature	 	 
	 	 	 
		 	 
	Print
    Name	 	 
	 	 	 
	President	 	 	 
	Position
    in Company	 	 

 

	Address
    for Notice:	 	 
	 	 	 
	1825 NW Corporate Blvd. #110	 	 	 
	 	 	 
	Boca Raton, FL 33431	 	 	 

 

	 
	 	 
	Number
    of shares of Common Stock
	

 

	 	 
	Number
    of shares of Common Stock underlying subject to warrants, options, debentures or other convertible securities

 

By
signing below, the Company each agrees to enforce the restrictions on transfer set forth in this Letter Agreement.

 

	CURATIVE
    BIOTECHNOLOGY, INC. 

     
	 
	 	 
	By:		 
	Name:	Richard
    Garr	 
	Title:	CEOExhibit
10.22

 

PUBLIC
HEALTH SERVICE

 

COOPERATIVE
RESEARCH AND DEVELOPMENT AGREEMENT

FOR
INTRAMURAL-PHS CLINICAL RESEARCH

 

This
Agreement is based on the model Cooperative Research and Development Agreement (“CRADA”) adopted by the U.S. Public Health
Service (“PHS”) Technology Transfer Policy Board for use by components of the National Institutes of Health (“NIH”),
the Centers for Disease Control and Prevention (“CDC”), and the Food and Drug Administration (“FDA”), which are
agencies of the PHS within the Department of Health and Human Services (“HHS”).

 

This
Cover Page identifies the Parties to this CRADA:

 

The
U.S. Department of Health and Human Services, as represented by

National
Eye Institute NEI,

an
Institute or Center (hereinafter referred to as the “IC”) of the

 

National
Institutes of Health

 

and

 

Curative
Biotechnology Holdings, Inc.

hereinafter
referred to as the “Collaborator”,

having
offices at

created
and operating under the laws of Florida.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 1 of 24		Revised October 18, 2018

    	 

    

 

COOPERATIVE
RESEARCH AND DEVELOPMENT AGREEMENT

FOR
INTRAMURAL-PHS CLINICAL RESEARCH

 

	Article
    1.	Introduction

 

This
CRADA between IC and Collaborator will be effective when signed by the Parties, which are identified on both the Cover Page and the Signature
Page. The official contacts for the Parties are identified on the Contacts Information Page. Publicly available information regarding
this CRADA appears on the Summary Page. The research and development activities that will be undertaken by IC and Collaborator in the
course of this CRADA are detailed in the Research Plan, attached as Appendix A. The staffing, funding, and materials contributions of
the Parties are set forth in Appendix B. This CRADA, including but not limited to all provisions with respect to the creation and/or
disposition of intellectual property, shall not alter the terms or rights granted to Collaborator under L-088-2021-0. All terms and conditions
of L-088-2021-0 remain binding and in effect.

 

	Article
    2.	Definitions

 

The
terms listed in this Article will carry the meanings indicated throughout the CRADA. To the extent a definition of a term as provided
in this Article is inconsistent with a corresponding definition in the applicable sections of either the United States Code (U.S.C.)
or the Code of Federal Regulations (C.F.R.), the definition in the U.S.C. or C.F.R. will control.

 

	 	“Adverse
    Event” or “AE” means any untoward medical occurrence associated with the use of a Test Article in humans,
    whether or not considered related to the Test Article (21 C.F.R §§ 312.32; see also E6(R2): Good Clinical Practice: Integrated
    Addendum to International Council for Harmonisation (ICH) E6(R1) Guidance for Industry, 83 Federal Register 8882 (2018).
	 	 
	 	“Affiliate”
    means any corporation or other business entity controlled by, controlling, or under common control with Collaborator at any time
    during the term of the CRADA. For this purpose, “control” means direct or indirect beneficial ownership of at least fifty
    percent (50%) of the voting stock or at least fifty percent (50%) interest in the income of the corporation or other business entity.
	 	 
	 	“Annual
    Report” means the report of progress of an IND-associated investigation that IC, as the IND Sponsor, must submit to the
    FDA within sixty (60) days of the anniversary of the effective date of the IND (pursuant to 21 C.F.R.§ 312.33).
	 	 
	 	“Background
    Invention” means an Invention conceived and first actually reduced to practice before the Effective Date.
	 	 
	 	“Certificate
    of Confidentiality” or “CoC” means a certificate issued by NIH pursuant to Section 301(d) of the Public
    Health Service Act (42 U.S.C. 241(d)), that protects the privacy of Human Subjects enrolled in the Protocol. With limited exceptions
    defined in 42 U.S.C. 241(d), the CoC protects from disclosure names or any information, documents or biospecimens containing ISI
    collected under a Protocol conducted under this CRADA.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 2 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	 	“Clinical
    Investigator” means, in accordance with 21 C.F.R. § 312.3, an individual who actually conducts a clinical investigation,
    that is, who directs the administration or dispensation of Test Article to a subject, and who assumes responsibility for studying
    Human Subjects, for recording and ensuring the integrity of research data, and for protecting the welfare and safety of Human Subjects.
	 	 
	 	“Collaborator
    Materials” means all tangible materials not first produced in the performance of this CRADA that are owned or controlled
    by Collaborator and used in the performance of the Research Plan. The term “Collaborator Materials” does not include
    “Test Article” (defined below).
	 	 
	 	“Confidential
    Information” means confidential scientific, business, financial information, or Identifiable, Sensitive Information provided
    that the information does not include:

 

	 	(a)	information
    that is publicly known or that is available from public sources;
	 	(b)	information
    that has been made available by its owner to others without a confidentiality obligation;
	 	(c)	information
    that is already known by the receiving Party, or information that is independently created or compiled by the receiving Party without
    reference to or use of the provided information; or
	 	(d)	information
    that relates to potential hazards or cautionary warnings associated with the production, handling, or use of the subject matter of
    the Research Plan.

 

	 	“Cooperative Research
    and Development Agreement” or “CRADA” means this Agreement, entered into pursuant to the Federal Technology
    Transfer Act of 1986, as amended (15 U.S.C. §§ 3710a et seq.), and Executive Order 12591 of April 10, 1987.
	 	 
	 	“CRADA Data”
    means all recorded information first produced in the performance of the Research Plan.
	 	 
	 	“CRADA Materials”
    means all tangible materials first produced in the performance of the Research Plan other than CRADA Data. For the avoidance of doubt,
    CRADA Materials do not include Collaborator Materials, IC Materials, Test Article, or specimens collected from Human Subjects.
	 	 
	 	“CRADA Principal
    Investigator(s)” or “CRADA PI(s)” means the person(s) designated by the Parties who will be responsible
    for the scientific and technical conduct of the Research Plan. The CRADA PI may also be a Clinical Investigator.
	 	 
	 	“CRADA Subject
    Invention” means any Invention of either or both Parties, conceived or first actually reduced to practice in the performance
    of the Research Plan.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 3 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	 	“Drug Master File”
    or “DMF” is described in 21 C.F.R. Part 314.420. A DMF is a submission to the FDA that may be used to provide
    confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and
    storing of one or more human drugs.
	 	 
	 	“Effective Date”
    means the date of the last signature of the Parties executing this Agreement.
	 	 
	 	“Government”
    means the Government of the United States of America.
	 	 
	 	“Human Subject”
    means, in accordance with the definition in 45 C.F.R. § 46.102(e)(1), a living individual about whom an investigator (whether
    professional or student) conducting research (i) obtains information or biospecimens through intervention or interaction with the
    individual, and uses, studies, or analyzes the information or biospecimens; or (ii) obtains, uses, studies, analyzes, or generates
    Identifiable Private Information or identifiable biospecimens.
	 	 
	 	“IC Materials”
    means all tangible materials not first produced in the performance of this CRADA that are owned or controlled by IC and used in the
    performance of the Research Plan.
	 	 
	 	“IND”
    means an “Investigational New Drug Application”, filed in accordance with 21 C.F.R. Part 312 under which
    clinical investigation of an experimental drug or biologic (Test Article) is performed in Human Subjects in the United States or
    intended to support a United States licensing action.
	 	 
	 	“Identifiable
    Private Information” or “IPI” about a Human Subject means private information for which the identity
    of the subject is or may readily be ascertained by the investigator or associated with the information. Regulations defining and
    governing this information include 45 C.F.R. Part 46.
	 	 
	 	“Identifiable,
    Sensitive Information” or “ISI” means, in accordance with the definition of 42 U.S.C. 241(d)(4), information
    that is about an individual and that is gathered or used during the course of research as described in 42 U.S.C. 241(d)(1)(A) through
    which an individual is identified, or that includes IPI, or for which there is at least a very small risk, as determined by current
    scientific practices or statistical methods, that some combination of the information, a request for the information, and other available
    data sources could be used to deduce the identity of an individual.
	 	 
	 	“Institutional
    Review Board” or “IRB” means, in accordance with 45 C.F.R. Part 46, 21 C.F.R. Part 56, and other applicable
    regulations, an independent body comprising medical, scientific, and nonscientific members, whose responsibility is to ensure the
    protection of the rights, safety, and well-being of the Human Subjects involved in a study.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 4 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	 	“Invention”
    means any invention or discovery that is or may be patentable or otherwise protected under Title 35 of the United States Code, or
    any novel variety of plant which is or may be protectable under the Plant Variety Protection Act, 7 U.S.C. §§ 2321 et
    seq.
	 	 
	 	“Investigator’s
    Brochure” means, in accordance with the definition in 21 C.F.R. § 312.23(a)(5), a document containing information
    about the Test Article, including animal screening, preclinical toxicology, and detailed pharmaceutical data, including a description
    of possible risks and side effects to be anticipated on the basis of prior experience with the drug or related drugs, and precautions,
    such as additional monitoring, to be taken as part of the investigational use of the drug.
	 	 
	 	“L-088-2021-0”
    means exclusive patent license NIH reference number L-088-2021-0 signed February 2, 2021 between the NIH-NEI and Curative Biotechnology
    Holdings, Inc.
	 	 
	 	“Patent Application”
    means an application for patent protection for a CRADA Subject Invention with the United States Patent and Trademark Office (“U.S.P.T.O.”)
    or the corresponding patent-issuing authority of another nation.
	 	 
	 	“Patent”
    means any issued United States patent, any international counterpart(s), and any corresponding grant(s) by a non-U.S. government
    in place of a patent.
	 	 
	 	“Placebo”
    means an inactive substance identical in appearance to the material being tested that is used to distinguish between drug action
    and suggestive effect of the material under study.
	 	 
	 	“Protocol”
    means the formal, detailed description of a study to be performed as provided for in the Research Plan. It describes the objective(s),
    design, methodology, statistical considerations, and organization of a trial. For the purposes of this CRADA, the term, Protocol,
    for clinical research involving Human Subjects, includes any and all associated documents, including informed consent forms, to be
    provided to Human Subjects and potential participants in the study.
	 	 
	 	“Raw Data”
    means the primary quantitative and empirical data first collected from experiments and clinical trials conducted within the scope
    of this CRADA.
	 	 
	 	“Research Plan”
    means the statement in Appendix A of the respective research and development commitments of the Parties. The Research Plan should
    describe the provisions for sponsoring the IND, clinical and safety monitoring, and data management.
	 	 
	 	“Sponsor”
    means, in accordance with the definition in 21 C.F.R. § 312.3, an organization or individual who assumes legal responsibility
    for supervising or overseeing clinical trials with Test Articles and is sometimes referred to as the IND holder.
	 	 
	 	“Steering Committee”
    means the research and development team whose composition and responsibilities with regard to the research performed under this CRADA
    are described in Appendix A.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 5 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	 	“Summary Data”
    means any extract or summary of the Raw Data, generated either by, or on behalf of, IC or by, or on behalf of, Collaborator. Summary
    Data may include extracts or summaries that incorporate ISI.
	 	 
	 	“Suspected Adverse
    Reaction” or “SAR” means any Adverse Event for which there is a reasonable possibility that the drug
    caused the Adverse Event. For the purposes of IND safety reporting, “reasonable possibility” means there is evidence
    to suggest a causal relationship between the drug and the Adverse Event. Suspected Adverse Reaction implies a lesser degree of certainty
    about causality than adverse reaction, which means any Adverse Event caused by a drug (21 CFR 312.32(a)).
	 	 
	 	“Test Article”
    means, in accordance with 21 C.F.R. § 50.3 (j), any drug (including a biological product), medical device, food additive, color
    additive, electronic product, or any other article subject to regulation under the Federal Food, Drug, and Cosmetic Act that is intended
    for administration to humans or animals, including a drug or biologic as identified in the Research Plan and Appendix B, that is
    used within the scope of the Research Plan. The Test Article may also be referred to as Investigational Agent, Study Material, or
    Study Product.
	 	 
	 	“Unique Ingredient
    Identifier” or “UNII” means a non-proprietary, free, unique, unambiguous, non-semantic, alphanumeric
    identifier based on a substance’s molecular structure and/or descriptive information and generated by the Global Registration
    System of the FDA.

 

	Article
    3.	Cooperative
    Research and Development

 

	3.1	Performance
    of Research and Development. The research and development activities to be carried out under this CRADA will be performed solely
    by the Parties identified on the Cover Page, unless specifically stated elsewhere in the Agreement. The CRADA PIs will be responsible
    for coordinating the scientific and technical conduct of this project on behalf of their employers. Any Collaborator employees who
    will work at IC facilities will be required to sign an agreement appropriately modified in view of the terms of this CRADA.
	 	 
	3.2	Research
    Plan. The Parties recognize that the Research Plan describes the collaborative research and development activities they will
    undertake and that interim research goals set forth in the Research Plan are good faith guidelines. Should events occur that require
    modification of these goals, then by mutual agreement the Parties can modify them through an amendment, according to Paragraph 13.6.
	 	 
	3.3	Use
    and Disposition of Collaborator Materials and IC Materials. The Parties agree to use Collaborator Materials and IC Materials
    only in accordance with the Research Plan and Protocol(s), not to transfer these materials to third parties except in accordance
    with the Research Plan and Protocol(s) or as approved by the owning or providing Party, and, upon expiration or termination of the
    CRADA, to dispose of these materials as directed by the owning or providing Party.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 6 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	3.4	Third-Party
    Rights in Collaborator’s CRADA Subject Inventions. If Collaborator has received (or will receive) support of any kind from
    a third party in exchange for rights in any of Collaborator’s CRADA Subject Inventions, Collaborator agrees to ensure that
    its obligations to the third party are both consistent with Articles 6 through 8 and subordinate to Article 7 of this CRADA.
	 	 
	3.5	Disclosures
    to IC. Prior to execution of this CRADA, Collaborator agrees to disclose to IC all instances in which outstanding royalties are
    due under a PHS license agreement and in which Collaborator had a PHS license terminated in accordance with 37 C.F.R. § 404.10.
    These disclosures will be treated as Confidential Information upon request by Collaborator in accordance with the definition in Article
    2 and Paragraphs 8.3 and 8.4.
	 	 
	3.6	Clinical
    Investigator Responsibilities. The Clinical Investigator will be required to submit, or to arrange for submission of, each Protocol
    associated with this CRADA to the IRB. In addition to the Protocol all associated documents, including informational documents and
    advertisements, must be reviewed and approved by the IRB before starting the research. The research will be done in strict accordance
    with the Protocol(s) and no substantive changes in a finalized Protocol will be made unless mutually agreed upon, in writing, by
    the Parties. Research will not commence (or will continue unchanged, if already in progress) until each substantive change to a Protocol,
    including those required by either the FDA or the IRB, has been integrated in a way acceptable to the Parties, submitted to the FDA
    (if applicable) and approved by the IRB.

 

	3.7	Investigational
    Applications.

 

	 	3.7.1	If
    an IND is required, IC will be the IND Sponsor and will submit an IND. All Clinical Investigators must have completed registration
    documents on file (1572 forms).
	 	 	 
	 	3.7.2	When
    IC files the IND, Collaborator agrees to provide IC background data and information necessary to support the IND in electronic Common
    Technical Document (eCTD) format: Suspected Adverse Reactions; and formulation and preclinical data, including toxicology findings.
    Collaborator further agrees to provide a letter of cross-reference to all pertinent regulatory filings sponsored by Collaborator.
    Collaborator’s employees will be reasonably available to respond to inquiries from the FDA regarding information and data contained
    in the Collaborator’s IND, DMF, other filings, or other information and data provided to IC by the Collaborator pursuant to
    this Article 3.
	 	 	 
	 	3.7.3	At
    least annually, the Collaborator will review the Investigator’s Brochure (IB) and will provide the updated IB in eCTD format,
    or if necessary, confirmation that no updates were made to the IB.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 7 of 24	Confidential	Revised October 18, 2018

    	 

    

 

	 	3.7.4	If
    Collaborator supplies Confidential Information to IC in support of an IND filed by IC, this information will be protected in accordance
    with the corresponding confidentiality provisions of Article 8.
	 	 	 
	 	3.7.5	Collaborator
    may sponsor its own clinical trials and hold its own IND for studies performed outside the scope of this CRADA. These studies, however,
    should not adversely affect the ability to accomplish the goal of the Research Plan, for example, by competing for the same study
    population. All data from those clinical trials are proprietary to Collaborator for purposes of this CRADA.

 

	3.8	Test
    Article Information and Supply.

 

	 	3.8.1	Collaborator
    agrees to provide IC without charge and on a schedule that will ensure adequate and timely performance of the research, a sufficient
    quantity of formulated and acceptably labeled, clinical-grade Test Article (and, as required by the Protocol(s), Placebo) to complete
    the clinical trial(s) agreed to and approved under this CRADA. If applicable, Collaborator agrees to provide Test Article labels
    to the IC. Collaborator will provide a Certificate of Analysis (COA) to IC in advance of an IND filing and for each lot of the Test
    Article provided.
	 	 	 
	 	3.8.2	The
    Test Article must be received by the IC in usable condition and accompanied by specific storage and shipping instructions, Material
    Safety Data Sheet (MSDS), a signed and dated COA, and stability or expiration dating information for each lot of Test Article sent.
    If the Collaborator performs ongoing stability testing for each lot of Test Article sent, then the Collaborator will also provide
    updated retest or expiration dates for those respective lots to the IC in a timely manner.
	 	 	 
	 	3.8.3	If
    there is evidence that the Test Article that arrived at the IC has not been maintained according to the defined shipping instructions
    or there is evidence of damage to the Test Article container or container closure system, IC will contact the Collaborator to inform
    them of the condition of the received Test Article and to determine together with the Collaborator whether the Test Article is usable
    or if it must be replaced. During the course of the clinical studies, the same process will be used whenever there is evidence that
    the Test Article has not been maintained according to the Collaborator’s recommended storage conditions. If the Test Article
    must be replaced, the Collaborator will replace it at no cost to IC.

 

	3.9	Test
    Article Delivery and Usage. Collaborator will ship the Test Article and, if required, Placebo to IC in containers marked in accordance
    with 21 C.F.R. § 312.6. IC agrees that the Clinical Investigators will keep appropriate records and take reasonable steps to
    ensure that the Test Article is used in accordance with the Protocol(s) and applicable FDA regulations. In addition, IC agrees that
    the Test Article (and all Confidential Information supplied by Collaborator relating to the Test Article) will be used solely for
    the conduct of the CRADA research and development activities. Furthermore, IC agrees that no analysis or modification of the Test
    Article will be performed without Collaborator’s prior written consent. At the completion of the Research Plan, any unused
    quantity of Test Article will be returned to Collaborator or disposed as directed by Collaborator. Pharmacy contacts at IC will be
    determined by IC and communicated to Collaborator.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
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	3.10	Monitoring.
    Subject to the restrictions in the Rights of Access and Publications section and the Certificate of Confidentiality Obligations
    section, and with reasonable advance notice and at reasonable times, IC will permit Collaborator or its designee(s) to audit
    the clinical monitoring performed by the IC, as well as to audit source documents containing Raw Data, to the extent necessary to
    verify compliance with the Protocol(s) and E6(R2): Good Clinical Practice: Integrated Addendum to International Council for Harmonisation
    (ICH) E6(R1) Guidance for Industry, 83 Federal Register 8882 (2018). Concerning the review and auditing of Raw Data and the exchange
    of CRADA Data, Collaborator agrees to accept the data processes, timelines, and deliverables of the IC.

 

	3.11	FDA
    Meetings/Communications.

 

(A)
Formal meetings with the FDA concerning the design of the clinical studies and/or data will be discussed and agreed upon in advance by
the Collaborator and the IC. The Collaborator will have the right to participate in all formal meetings with the FDA as appropriate.
The Collaborator agrees not to contact the FDA independent of the IC concerning the clinical studies under this Agreement. However, the
Collaborator may contact the FDA on separate product-related issues.

 

(B)
The Collaborator will promptly notify the IC of the following: (1) any FDA correspondence related to the Protocol that is received by
the Collaborator or its Affiliates; and (2) any FDA enforcement actions directed toward the Collaborator or its Affiliates related to
the Protocol.

 

(C)
The Collaborator will also promptly notify the IC of any action taken by the FDA regarding manufacturing of the Test Article that would
impact the safety of Human Subjects participating in the study.

 

	Article
    4.	Reports

 

	4.1	Interim
    Research and Development Reports. The CRADA PIs should exchange information regularly, in writing. This exchange may be accomplished
    through meeting minutes, detailed correspondence, circulation of draft manuscripts, Steering Committee reports, copies of Annual
    Reports and any other reports updating the progress of the CRADA research. However, the Parties must exchange updated Investigator’s
    Brochure, formulation and preclinical data, and toxicology findings, as they become available these data and documents will be provided
    in eCTD format, except for IC’s preclinical data that will be provided in standard laboratory data format.
	 	 
	4.2	Final
    Research and Development Reports. The Parties will exchange final reports of their results within six (6) months after the expiration
    or termination of this CRADA. These reports will set forth the technical progress made; any publications arising from the research;
    and the existence of invention disclosures of potential CRADA Subject Inventions and/or any corresponding Patent Applications.

 

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	4.3	Fiscal
    Reports. If Collaborator has agreed to provide funding to IC under this CRADA and upon the request of Collaborator, then concurrent
    with the exchange of final research and development reports according to Paragraph 4.2, IC will submit to Collaborator a statement
    of all costs incurred by IC for the CRADA. If the CRADA has been terminated, IC will specify any costs incurred before the date of
    termination for which IC has not received funds from Collaborator, as well as for all reasonable termination costs including the
    cost of returning Collaborator property or removal of abandoned Collaborator property, for which Collaborator will be responsible.

 

	4.4	Safety
    Reports.

 

4.4.1
In accordance with FDA requirements IC, as the IND Sponsor, will establish and maintain records and submit safety reports to the FDA,
as required by 21 C.F.R. § 312.32 and 21 C.F.R. § 812.150(b)(1), or other applicable Federal regulations. In the conduct of
research under this CRADA, the Parties will comply with specific IC guidelines and policies for reporting AEs. IC must provide Collaborator
with copies of all Safety Reports concurrently with their submission to the FDA, and with any other information affecting the safety
of Human Subjects in research conducted under this CRADA.

 

4.4.2
During and for a period of two years after the completion of a Protocol, the Collaborator shall promptly provide to the IC any information
that Collaborator has reasonably determined could directly affect the health or safety of past or current Human Subjects or influence
the conduct of the Protocol. Such information may arise from any source, for example, Safety Reports provided to the FDA, study results,
information in site monitoring reports or data safety monitoring committee reports. IC shall be free to communicate the relevant safety
information to each Human Subject and the IRB.

 

	4.5	Annual
    Reports. IC will provide Collaborator a copy of the Annual Report concurrently with the submission of the Annual Report to the
    FDA. Annual Reports will be kept confidential in accordance with Article 8.

 

	Article
    5.	Staffing,
    Financial, and Materials Obligations

 

	5.1	IC
    and Collaborator Contributions. The contributions of any staff, funds, materials, and equipment by the Parties are set forth
    in Appendix B. The Federal Technology Transfer Act of 1986, 15 U.S.C. § 3710a(d)(1) prohibits IC from providing funds to Collaborator
    for any research and development activities under this CRADA.
	 	 
	5.2	IC
    Staffing. No IC employees will devote 100% of their effort or time to the research and development activities under this CRADA.
    IC will not use funds provided by Collaborator under this CRADA for IC personnel to pay the salary of any permanent IC employee.
    Although personnel hired by IC using CRADA funds will focus principally on CRADA research and development activities, Collaborator
    acknowledges that these personnel may nonetheless make contributions to other research and development activities, and the activities
    will be outside the scope of this CRADA.

 

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	5.3	Collaborator
    Funding. Collaborator acknowledges that Government funds received by Collaborator from an agency of the Department of Health
    and Human Services may not be used to fund IC under this CRADA. If Collaborator has agreed to provide funds to IC, then the payment
    schedule appears in Appendix B and Collaborator will make payments according to that schedule. If Collaborator fails to make any
    scheduled payment, IC will not be obligated to perform any of the research and development activities specified herein or to take
    any other action required by this CRADA until the funds are received. IC will use these funds exclusively for the purposes of this
    CRADA. Each Party will maintain separate and distinct current accounts, records, and other evidence supporting its financial obligations
    under this CRADA and, upon written request, will provide the other Party a Fiscal Report according to Paragraph 4.3, which delineates
    all payments made and all obligated expenses, along with the Final Research Report described in Paragraph 4.2.
	 	 
	5.4	Capital
    Equipment. Collaborator’s commitment, if any, to provide IC with capital equipment to enable the research and development
    activities under the Research Plan appears in Appendix B. If Collaborator transfers to IC the capital equipment or provides funds
    for IC to purchase it, then IC will own the equipment. If Collaborator loans capital equipment to IC for use during the CRADA, Collaborator
    will be responsible for paying all costs and fees associated with the transport, installation, maintenance, repair, removal, or disposal
    of the equipment, and IC will not be liable for any damage to the equipment.

 

	Article
    6.	Intellectual
    Property

 

	6.1	Ownership
    of CRADA Subject Inventions, CRADA Data, and CRADA Materials. Subject to the Government license described in Paragraph 7.5, the
    sharing requirements of Paragraph 8.1 and the regulatory filing requirements of Paragraph 8.2, the inventing Party will retain sole
    ownership of and title to all CRADA Subject Inventions invented solely by its employee(s), and the producing Party will retain all
    copies of CRADA Data, and all CRADA Materials produced solely by its employee(s). The Parties will own jointly all CRADA Subject
    Inventions invented jointly and all CRADA Materials developed jointly.
	 	 
	6.2	Reporting.
    The Parties will promptly report to each other in writing each CRADA Subject Invention reported by their respective personnel, and
    any Patent Applications filed thereon, resulting from the research and development activities conducted under this CRADA. Each Party
    will report all CRADA Subject Inventions to the other Party in sufficient detail to determine inventor ship, which will be determined
    in accordance with U.S. patent law. These reports will be treated as Confidential Information in accordance with Article 8. Formal
    reports will be made by and to the Patenting and Licensing Offices identified on the Contacts Information Page herein.

 

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	6.3	Filing
    of Patent Applications. Each Party will make timely decisions regarding the filing of Patent Applications on the CRADA Subject
    Inventions made solely by its employee(s) and will notify the other Party in advance of filing. Collaborator will have the first
    opportunity to file a Patent Application on joint CRADA Subject Inventions and will notify PHS of its decision within sixty (60)
    days of an Invention being reported or at least thirty (30) days before any patent filing deadline, whichever occurs sooner. If Collaborator
    fails to notify PHS of its decision within that time period or notifies PHS of its decision not to file a Patent Application, then
    PHS has the right to file a Patent Application on the joint CRADA Subject Invention. Neither Party will be obligated to file a Patent
    Application. Each Party will provide the other Party with a final draft of any Patent Application on the CRADA Subject Invention
    thirty (30) days before filing so that the other Party can review and ensure protection of its Confidential Information unless a
    rush filing is necessary. A rush filing means the filing of a Patent Application, due to an impending, enabling disclosure, e.g.,
    publication of a journal article or a presentation at a public event, the timing of which may not allow for the thirty (30) day review
    period. In the case of a rush filing where a thirty-day review period is not available, each Party will use reasonable efforts to
    discuss such Patent Application with the other Party reasonably in advance of the rush filing of such Patent Application. Neither
    Party’s Confidential Information shall be included or disclosed in any Patent Application without the other Party’s express
    prior written consent. Collaborator will place the following statement in any Patent Application it files on a CRADA Subject Invention:
    “This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes
    of Health, an Agency of the Department of Health and Human Services. The Government of the United States has certain rights in this
    invention.” If either Party files a Patent Application on a joint CRADA Subject Invention, then the filing Party will include
    a statement within the Patent Application that clearly identifies the Parties and states that the joint CRADA Subject Invention was
    made under this CRADA.
	 	 
	6.4	Patent
    Expenses. Unless agreed otherwise, the Party filing a Patent Application will pay all preparation and filing expenses, prosecution
    fees, issuance fees, post issuance fees, patent maintenance fees, annuities, interference expenses, and attorneys’ fees for
    that Patent Application and any resulting Patent(s). If a license to any CRADA Subject Invention is granted to Collaborator, then
    Collaborator will be responsible for all expenses and fees, past and future, in connection with the preparation, filing, prosecution,
    and maintenance of any Patent Applications and Patents claiming exclusively licensed CRADA Subject Inventions and will be responsible
    for a pro-rated share, divided equally among all licensees, of those expenses and fees for non-exclusively licensed CRADA Subject
    Inventions. Collaborator may waive its exclusive option rights at any time and incur no subsequent financial obligation for those
    Patent Application(s) or Patent(s).
	 	 
	6.5	Prosecution
    of Patent Applications. The Party filing a Patent Application will provide the non-filing Party with a copy of any official communication
    relating to prosecution of the Patent Application within thirty (30) days of transmission of the communication. Each Party will also
    provide the other Party with the power to inspect and make copies of all documents retained in the applicable Patent Application
    or Patent file. The Parties agree to consult with each other regarding the prosecution of Patent Applications directed to joint CRADA
    Subject Inventions. If Collaborator elects to file and prosecute Patent Applications on joint CRADA Subject Inventions, then Collaborator
    agrees to use the U.S.P.T.O. Customer Number Practice and/or grant PHS a power(s) of attorney (or equivalent) necessary to assure
    PHS access to its intellectual property rights in these Patent Applications. PHS and Collaborator will cooperate with each other
    to obtain necessary signatures on Patent Applications, assignments, or other documents.

 

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	Article
    7.	Licensing

 

	7.1	Background
    Inventions. Other than as specifically stated in this Article 7, nothing in this CRADA will be construed to grant any rights
    in one Party’s Background Invention(s) to the other Party, except to the extent necessary for the Parties to conduct the research
    and development activities described in the Research Plan
	 	 
	7.2	Collaborator’s
    License Option to CRADA Subject Inventions. With respect to Government rights to any CRADA Subject Invention made solely by an
    IC employee(s) or made jointly by an IC employee(s) and a Collaborator employee(s) for which a Patent Application was filed, PHS
    hereby grants to Collaborator an exclusive option to elect an exclusive or nonexclusive commercialization license. The license will
    be substantially in the form of the appropriate model PHS license agreement and will fairly reflect the nature of the CRADA Subject
    Invention, the relative contributions of the Parties to the CRADA Subject Invention and the CRADA, a plan for the development and
    marketing of the CRADA Subject Invention, the risks incurred by Collaborator, and the costs of subsequent research and development
    needed to bring the CRADA Subject Invention to the marketplace. The field of use of the license will not exceed the scope of the
    Research Plan.
	 	 
	7.3	Exercise
    of Collaborator’s License Option. To exercise the option of Paragraph 7.2 Collaborator must submit a written notice to
    the PHS Patenting and Licensing Contact identified on the Contacts Information Page (and provide a copy to the IC Contact for CRADA
    Notices) within three (3) months after either (i) Collaborator receives written notice from PHS that the Patent Application has been
    filed or (ii) the date on which Collaborator files the Patent Application. The written notice exercising this option will include
    a completed “Application for License to Public Health Service Inventions” and will initiate a negotiation period that
    expires nine (9) months after the exercise of the option. PHS and Collaborator will negotiate in good faith during the nine (9) month
    negotiation period. If PHS has not responded in writing to the last proposal by Collaborator within this nine (9) month period, the
    negotiation period will be extended to expire one (1) month after PHS so responds, during which month Collaborator may accept in
    writing the final license proposal of PHS. In the absence of Collaborator’s exercise of the option, or upon election of a nonexclusive
    license, PHS will be free to license the CRADA Subject Invention to others. In the event that Collaborator elects the option for
    an exclusive license, but no such license is executed during the negotiation period, PHS agrees not to make an offer on more favorable
    terms to a third party for a period of nine (9) months without first offering Collaborator the same terms to be offered to the third
    party, in which case Collaborator shall have a period of thirty (30) days in which to accept or reject the offer. These time periods
    may be extended at the sole discretion of PHS upon good cause shown in writing by Collaborator.

 

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	7.4	Government
    License in IC Sole CRADA Subject Inventions and Joint CRADA Subject Inventions. Pursuant to 15 U.S.C. § 3710a(b)(1)(A),
    for CRADA Subject Inventions owned solely by IC or jointly by IC and Collaborator, and licensed pursuant to the option of Paragraph
    7.2, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up license to practice the CRADA Subject
    Invention or have the CRADA Subject Invention practiced throughout the world by or on behalf of the Government. In the exercise of
    this license, the Government will not publicly disclose trade secrets or commercial or financial information that is privileged or
    confidential within the meaning of 5 U.S.C. § 552(b)(4) or which would be considered privileged or confidential if it had been
    obtained from a non-federal party.
	 	 
	7.5	Government
    License in Collaborator Sole CRADA Subject Inventions. Pursuant to 15 U.S.C. § 3710a(b)(2), for CRADA Subject Inventions
    made solely by an employee of Collaborator, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up
    license to practice the CRADA Subject Invention or have the CRADA Subject Invention practiced throughout the world by or on behalf
    of the Government for research or other Government purposes.
	 	 
	7.6	Third
    Party License. Pursuant to 15 U.S.C. § 3710a(b)(1)(B), if PHS grants Collaborator an exclusive license to a CRADA Subject
    Invention made solely by an IC employee or jointly with a Collaborator employee, the Government will retain the right to require
    Collaborator to grant to a responsible applicant a nonexclusive, partially exclusive, or exclusive sublicense to use the CRADA Subject
    Invention in Collaborator’s licensed field of use on terms that are reasonable under the circumstances; or, if Collaborator
    fails to grant a license, to grant a license itself. The exercise of these rights by the Government will only be in exceptional circumstances
    and only if the Government determines (i) the action is necessary to meet health or safety needs that are not reasonably satisfied
    by Collaborator, (ii) the action is necessary to meet requirements for public use specified by federal regulations, and such requirements
    are not reasonably satisfied by Collaborator; or (iii) Collaborator has failed to comply with an agreement containing provisions
    described in 15 U.S.C. § 3710a(c)(4)(B). The determination made by the Government under this Paragraph is subject to administrative
    appeal and judicial review under 35 U.S.C. § 203(b).
	 	 
	7.7	Third-Party
    Rights In IC Sole CRADA Subject Inventions. For a CRADA Subject Invention conceived prior to the Effective Date solely by an
    IC employee that is first actually reduced to practice after the Effective Date in the performance of the Research Plan, the option
    offered to Collaborator in Paragraph 7.2 may be restricted if, prior to the Effective Date, PHS had filed a Patent Application and
    has either offered or granted a license in the CRADA Subject Invention to a third party. Collaborator nonetheless retains the right
    to apply for a license to any such CRADA Subject Invention in accordance with the terms and procedures of 35 U.S.C. § 209 and
    37 C.F.R. Part 404.

 

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	Article
    8.	Rights
    of Access and Publication

 

	8.1	Right of Access to CRADA
    Data and CRADA Materials. IC and Collaborator agree to exchange all CRADA Data and to share all CRADA Materials. If the CRADA
    is terminated, both Parties agree to provide CRADA Materials in quantities needed to complete the Research Plan. Such provision will
    occur before the termination date of the CRADA or sooner, if required by the Research Plan. If Collaborator possesses any human biological
    specimens from clinical trials under the CRADA, the specimens must be handled as described in the Protocol or as otherwise directed
    by IC before the termination date of the CRADA.
	 	 
	8.2	Use of CRADA Data and
    CRADA Materials. The Parties will be free to utilize CRADA Data and CRADA Materials internally for their own purposes, consistent
    with their obligations under this CRADA. The Parties may share CRADA Data or CRADA Materials with their Affiliates, agents or contractors
    provided the obligations of this Article 8.2 are simultaneously conveyed.

 

	 	8.2.1	CRADA
    Data.

 

Collaborator
and IC will use reasonable efforts to keep CRADA Data confidential until published or until corresponding Patent Applications are filed.
To the extent permitted by law, each Party will have the right to use any and all CRADA Data in and for any regulatory filing by or on
behalf of the Party.

 

	 	8.2.2	CRADA
    Materials.

 

Collaborator
and IC do not anticipate that CRADA Materials will be generated in performance of the CRADA Research Plan. Biospecimens will be handled
in accordance with the Protocol.

 

	8.3	Confidential
    Information. Each Party agrees to limit its disclosure of Confidential Information to the amount necessary to carry out the Research
    Plan and will place a confidentiality notice on all this information. A Party orally disclosing Confidential Information to the other
    Party will summarize the disclosure in writing and provide it to the other Party within fifteen (15) days of the disclosure. Each
    Party receiving Confidential Information agrees to use it only for the purposes described in the Research Plan. Either Party may
    object to the designation of information as Confidential Information by the other Party.
	 	 
	8.4	Protection
    of Confidential Information. Confidential Information will not be disclosed, copied, reproduced or otherwise made available to
    any other person or entity without the consent of the owning or providing Party except as required by a court or administrative body
    of competent jurisdiction, or federal law or regulation. Each Party agrees to use reasonable efforts to maintain the confidentiality
    of Confidential Information, which will in no instance be less effort than the Party uses to protect its own Confidential Information.
    Each Party agrees that a Party receiving Confidential Information will not be liable for the disclosure of that portion of the Confidential
    Information which, after notice to and consultation with the disclosing Party, the receiving Party determines may not be lawfully
    withheld, provided the disclosing Party has been given a reasonable opportunity to seek a court order to enjoin disclosure.

 

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	8.5	Human
    Subject Protection. The research to be conducted under this CRADA involves Human Subjects or human tissues within the meaning
    of 45 C.F.R. Part 46, and all research to be performed under this CRADA will conform to applicable federal laws and regulations.
    Additional information is available from the HHS Office for Human Research Protections (http://www.hhs.gov/ohrp/).
	 	 
	8.6	Duration
    of Confidentiality Obligation. The obligation to maintain the confidentiality of Confidential Information will expire at the
    earlier of the date when the information is no longer Confidential Information as defined in Article 2 or five (5) years after the
    expiration or termination date of this CRADA, except for ISI, for which the obligation to maintain confidentiality will extend indefinitely.
    Collaborator may request an extension to this term when necessary to protect Confidential Information relating to products not yet
    commercialized.
	 	 
	8.7	Publication.
    The Parties are encouraged to make publicly available the results of their research and development activities. Before either Party
    submits a paper or abstract for publication or otherwise intends to publicly disclose information about a CRADA Subject Invention,
    CRADA Data, or CRADA Materials, including, without limitation, in a written publication, public presentation, or other public disclosure,
    the other Party will have thirty (30) days to review such proposed disclosure (or ten (10) days for an abstract) to assure that Confidential
    Information is protected. Either Party may request in writing that the proposed publication or other disclosure be delayed for up
    to forty-five (45) additional days as necessary to file a Patent Application. Neither Party’s Confidential Information shall
    be included or disclosed in any publication or other public disclosure without the providing Party’s express prior written
    consent.
	 	 
	8.8	Certificate
    of Confidentiality Obligations. Any ISI that Collaborator receives from NIH is covered by a CoC and therefore all copies of ISI
    are immune from the legal process, and will not, without the consent of the Human Subject, be admissible as evidence or used for
    any purpose in any action, suit, or other judicial, legislative, or administrative proceeding.

 

Notwithstanding
the forgoing, Collaborator will be permitted to disclose ISI:

 

	 	a.	If
    required by Federal, State, or local laws (e.g., as required by the Federal Food, Drug, and Cosmetic Act, or state laws requiring
    the reporting of communicable diseases to State and local health departments), excluding instances of disclosure in any Federal,
    State, or local civil, criminal, administrative, legislative, or other proceeding;
	 	 	 
	 	b.	If
    the consent of the Human Subject to whom the information, document, or biospecimen pertains obtained by the IC allowed for such disclosure.

 

Prior
to making any permitted disclosures above, Collaborator will ensure that any recipient of ISI protected by a CoC is aware of its confidential
nature and the requirement to comply with the CoC (see https://humansubjects.nih.gov/coc/background).

 

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	Article
    9.	Representations
    and Warranties

 

	9.1	Representations
    of IC. IC hereby represents to Collaborator that:

 

	 	9.1.1	IC
    has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that IC’s official
    signing this CRADA has authority to do so.
	 	 	 
	 	9.1.2	To
    the best of its knowledge and belief, neither IC nor any of its personnel involved in this CRADA is presently subject to debarment
    or suspension by any agency of the Government which would directly affect its performance of the CRADA. Should IC or any of its personnel
    involved in this CRADA be debarred or suspended during the term of this CRADA, IC will notify Collaborator within thirty (30) days
    of receipt of final notice.

 

	9.2	Representations
    and Warranties of Collaborator. Collaborator hereby represents and warrants to IC that:

 

	 	9.2.1	Collaborator
    has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that Collaborator’s
    official signing this CRADA has authority to do so.
	 	 	 
	 	9.2.2	Neither
    Collaborator nor any of its personnel involved in this CRADA, including Affiliates, agents, and contractors are presently subject
    to debarment or suspension by any agency of the Government. Should Collaborator or any of its personnel involved in this CRADA be
    debarred or suspended during the term of this CRADA, Collaborator will notify IC within thirty (30) days of receipt of final notice.
	 	 	 
	 	9.2.3	Subject
    to Paragraph 12.3, and if and to the extent Collaborator has agreed to provide funding under Appendix B, Collaborator is financially
    able to satisfy these obligations in a timely manner.
	 	 	 
	 	9.2.4	The
    Test Article provided has been produced, or will be produced if not already produced, in accordance with the FDA’s current
    Good Manufacturing Practice set out in 21 C.F.R. §§ 210-211 and ICH QA7, and meets the specifications cited in the Certificate
    of Analysis and Investigator’s Brochure provided.

 

	Article
    10.	Contingency,
    Expiration and Termination

 

	10.1	Contingency.
    Parties will review results of preclinical pharmacology and toxicology testing of the ocular metformin formulation. Only
    after the IC concludes that clinical studies can be safely commenced, will the clinical safety studies commence.
	 	 
	10.2	Expiration.
    This CRADA will expire on the last date of the term set forth on the Summary Page. In no case will the term of this CRADA extend
    beyond the term indicated on the Summary Page unless it is extended in writing in accordance with Paragraph 13.6.

 

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	10.3	Termination
    by Mutual Consent. IC and Collaborator may terminate this CRADA at any time by mutual written consent.
	 	 
	10.4	Unilateral
    Termination. Either IC or Collaborator may unilaterally terminate this CRADA at any time by providing written notice at least
    sixty (60) days before the desired termination date. IC may, at its option, retain funds transferred to IC before unilateral termination
    by Collaborator for use in completing the Research Plan. If Collaborator terminates this Agreement before the completion of all approved
    or active Protocol(s), then Collaborator will supply enough Test Article (and Placebo, if applicable) necessary to complete these
    Protocol(s) unless termination is for safety concerns.
	 	 
	10.5	Funding
    for IC Personnel. If Collaborator has agreed to provide funding for IC personnel and this CRADA is mutually or unilaterally terminated
    by Collaborator before its expiration, then Collaborator agrees that funds for that purpose will be available to IC for a period
    of six (6) months after the termination date or until the expiration date of the CRADA, whichever occurs sooner. If there are insufficient
    funds to cover this expense, Collaborator agrees to pay the difference.
	 	 
	10.6	New
    Commitments. Neither Party will incur new expenses related to this CRADA after expiration, mutual termination, or a notice of
    a unilateral termination and will, to the extent feasible, cancel all outstanding commitments and contracts by the termination date.
    Collaborator acknowledges that IC will have the authority to retain and expend any funds for up to one (1) year subsequent to the
    expiration or termination date to cover any unpaid costs obligated during the term of the CRADA in undertaking the research and development
    activities set forth in the Research Plan.
	 	 
	10.7	Collaborator
    Failure to Continue Development. If Collaborator suspends development of the Test Article without the transfer of its active
    development efforts, assets, and obligations to a third party within ninety (90) days of discontinuation, Collaborator agrees that
    IC may continue developing the Test Article. In that event, the following will apply:

 

	 	10.7.1	Collaborator
    agrees to transfer to IC all information necessary to enable IC to contract for the manufacture of the Test Article and, unless abandoned
    for reasons relating to safety as determined by the data safety monitoring board, to provide the Test Article (and Placebo, if any)
    in Collaborator’s inventory to IC.
	 	 	 
	 	10.7.2	Further,
    Collaborator hereby grants to IC a nonexclusive, irrevocable, world- wide, paid-up license to practice, or have practiced for or
    on behalf of the Government, any Background Invention that Collaborator may currently have or will obtain on the Test Article, its
    manufacture, or on any method of using the Test Article for the indication(s) described in the Research Plan, including the right
    to sublicense to third parties.

 

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	Article
    11.	Disputes

 

	11.1	Settlement.
    Any dispute arising under this CRADA which is not disposed of by agreement of the CRADA Principal Investigators will be submitted
    jointly to the signatories of this CRADA. If the signatories, or their designees, are unable to jointly resolve the dispute within
    thirty (30) days after notification thereof, the Assistant Secretary for Health (or his/her designee or successor) will propose a
    resolution. Nothing in this Paragraph will prevent any Party from pursuing any additional administrative remedies that may be available
    and, after exhaustion of such administrative remedies, pursuing all available judicial remedies.
	 	 
	11.2	Continuation
    of Work. Pending the resolution of any dispute or claim pursuant to this Article 11, the Parties agree that performance of all
    obligations will be pursued diligently.

 

	Article
    12.	Liability

 

	12.1	NO
    WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER,
    INCLUDING THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR MATERIAL, WHETHER TANGIBLE OR INTANGIBLE, MADE OR DEVELOPED UNDER OR
    OUTSIDE THE SCOPE OF THIS CRADA, OR THE OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE RESEARCH OR ANY INVENTION
    OR MATERIAL, OR THAT A TECHNOLOGY UTILIZED BY A PARTY IN THE PERFORMANCE OF THE RESEARCH PLAN DOES NOT INFRINGE ANY THIRD-PARTY PATENT
    RIGHTS.
	 	 
	12.2	Indemnification
    and Liability. Collaborator agrees to hold the Government harmless and to indemnify the Government for all liabilities, demands,
    damages, expenses and losses arising out of the use by Collaborator for any purpose of the CRADA Data, CRADA Materials or CRADA Subject
    Inventions produced in whole or part by IC employees under this CRADA, unless due to the negligence or willful misconduct of IC,
    its employees, or agents. The Government has no statutory authority to indemnify Collaborator. Each Party otherwise will be liable
    for any claims or damages it incurs in connection with this CRADA, except that IC, as an agency of the Government, assumes liability
    only to the extent provided under the Federal Tort Claims Act , 28 U.S.C. Chapter 171.
	 	 
	12.3	Force
    Majeure. Neither Party will be liable for any unforeseeable event beyond its reasonable control and not caused by its own
    fault or negligence, which causes the Party to be unable to perform its obligations under this CRADA, and which it has been unable
    to overcome by the exercise of due diligence. If a force majeure event occurs, the Party unable to perform will promptly notify
    the other Party. It will use its best efforts to resume performance as quickly as possible and will suspend performance only for
    such period of time as is necessary as a result of the force majeure event.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
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	Article
    13.	Miscellaneous

 

	13.1	Governing
    Law. The construction, validity, performance and effect of this CRADA will be governed by U.S. federal law, as applied by the
    federal courts in the District of Columbia. If any provision in this CRADA conflicts with or is inconsistent with any U.S. federal
    law or regulation, then the U.S. federal law or regulation will preempt that provision.
	 	 
	13.2	Compliance
    with Law. IC and Collaborator agree that they will comply with, and advise any contractors, grantees, or agents they have engaged
    to conduct the CRADA research and development activities to comply with, all applicable Executive Orders, statutes, and HHS regulations
    relating to research on human subjects (45 C.F.R. Part 46, 21 C.F.R. Parts 50 and 56) and relating to the appropriate care and use
    of laboratory animals (7 U.S.C. § 2131 et seq.; 9 C.F.R. Part 1, Subchapter A). IC and Collaborator will advise any contractors,
    grantees, or agents they have engaged to conduct clinical trials for this CRADA that they must comply with all applicable federal
    regulations for the protection of Human Subjects, which may include the Standards for Privacy of Individually Identifiable Health
    Information set forth in 45 C.F.R. Part 164. Collaborator agrees to ensure that its employees, contractors, and agents who might
    have access to a “select agent or toxin” (as that term is defined in 42 C.F.R. §§ 73.4-73.5) transferred from
    IC is properly licensed to receive the “select agent or toxin”.
	 	 
	13.3	Waivers.
    None of the provisions of this CRADA will be considered waived by any Party unless a waiver is given in writing to the other Party.
    The failure of a Party to insist upon strict performance of any of the terms and conditions hereof, or failure or delay to exercise
    any rights provided herein or by law, will not be deemed a waiver of any rights of any Party.
	 	 
	13.4	Headings.
    Titles and headings of the articles and paragraphs of this CRADA are for convenient reference only, do not form a part of this CRADA,
    and will in no way affect its interpretation.
	 	 
	13.5	Severability.
    The illegality or invalidity of any provisions of this CRADA will not impair, affect, or invalidate the other provisions of this
    CRADA.
	 	 
	13.6	Amendments.
    Minor modifications to the Research Plan may be made by the mutual written consent of the CRADA Principal Investigators. Substantial
    changes to the CRADA or extensions of the term will become effective only upon a written amendment signed by the signatories to this
    CRADA or by their representatives duly authorized to execute an amendment. A change will be considered substantial if it directly
    expands the range of the potential CRADA Subject Inventions, alters the scope or field of any license option governed by Article
    7, or requires a significant increase in the contribution of resources by either Party.

 

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	13.7	Assignment.
    Neither this CRADA nor any rights or obligations of any Party hereunder shall be assigned or otherwise transferred by either Party
    without the prior written consent of the other Party, which consent shall not be unreasonably withheld, delayed or conditioned. For
    the avoidance of doubt, the foregoing limitations shall not apply to the assignment or transfer of this Agreement by Collaborator
    to an Affiliate in connection with an internal reorganization, and Collaborator will notify IC of such assignment in advance of such
    reorganization. The Collaborator acknowledges the applicability of 41 U.S.C. § 15, the Anti Assignment Act, to this Agreement.
    The Parties agree that the identity of the Collaborator is material to the performance of this CRADA and that the duties under this
    CRADA are nondelegable.
	 	 
	13.8	Notices.
    All notices pertaining to or required by this CRADA will be in writing, signed by an authorized representative of the notifying Party,
    and delivered by first class, registered, or certified mail, or by an express/overnight commercial delivery service, prepaid and
    properly addressed to the other Party at the address designated on the Contacts Information Page, or to any other address designated
    in writing by the other Party. Notices will be considered timely if received on or before the established deadline date or sent on
    or before the deadline date as verifiable by U.S. Postal Service postmark or dated receipt from a commercial carrier. Notices regarding
    the exercise of license options will be made pursuant to Paragraph 7.3. Either Party may change its address by notice given to the
    other Party in the manner set forth above.
	 	 
	13.9	Independent
    Contractors. The relationship of the Parties to this CRADA is that of independent contractors and not agents of each other or
    joint venturers or partners. Each Party will maintain sole and exclusive control over its personnel and operations.
	 	 
	13.10	Use
    of Name; Press Releases. By entering into this CRADA, the Government does not directly or indirectly endorse any product or service
    that is or will be provided, whether directly or indirectly related to either this CRADA or to any patent or other intellectual-
    property license or agreement that implements this CRADA by Collaborator, its successors, assignees, or licensees. Collaborator will
    not in any way state or imply that the Government or any of its organizational units or employees endorses any product or services.
    Each Party agrees to provide proposed press releases that reference or rely upon the work under this CRADA to the other Party for
    review and comment at least five (5) business days before publication. Either Party may disclose the Title and Abstract of the CRADA
    to the public without the approval of the other Party.
	 	 
	13.11	Reasonable
    Consent. Whenever a Party’s consent or permission is required under this CRADA, its consent or permission will not be unreasonably
    withheld.
	 	 
	13.12	Export
    Controls. Collaborator agrees to comply with U.S. export law and regulations. If Collaborator has a need to transfer any CRADA
    Materials made in whole or in part by IC, or IC Materials, or IC’s Confidential Information to a person located in a country
    other than the United States, to an Affiliate organized under the laws of a country other than the United States, or to an employee
    of Collaborator in the United States who is not a citizen or permanent resident of the United States, Collaborator will acquire any
    and all necessary export licenses and other appropriate authorizations.
	 	 
	13.13	Entire
    Agreement. This CRADA constitutes the entire agreement between the Parties concerning the subject matter of this CRADA and supersedes
    any prior understanding or written or oral agreement.
	 	 
	13.14	Survivability.
                                            The provisions of Paragraphs 3.3, 3.4, 3.8, 4.2, 4.3, 4.4.2, 5.3, 5.4, 6.1- 9.2, 10.4-10.7,
                                            11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.7, 13.10 and 13.14 will survive the expiration or early
                                            termination of this CRADA.

    

 

SIGNATURES
BEGIN ON THE NEXT PAGE

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 21 of 24	Confidential	Revised October 18, 2018

    	 

    

 

SIGNATURE
PAGE

 

ACCEPTED
AND AGREED

 

BY
EXECUTING THIS AGREEMENT, EACH PARTY REPRESENTS THAT ALL STATEMENTS MADE HEREIN ARE TRUE, COMPLETE, AND ACCURATE TO THE BEST OF ITS KNOWLEDGE.
COLLABORATOR ACKNOWLEDGES THAT IT MAY BE SUBJECT TO CRIMINAL, CIVIL, OR ADMINISTRATIVE PENALTIES FOR KNOWINGLY MAKING A FALSE, FICTITIOUS,
OR FRAUDULENT STATEMENT OR CLAIM.

 

	FOR
    IC:	 	 
	 	 	 
	/s/ Santa Tumminia	 	 
	Santa
    Tumminia, Ph.D.	 	Date
	Deputy Director, NEI	 	 

 

FOR
CURATIVE BIOTECHNOLOGY HOLDINGS, INC. (“COLLABORATOR”):

 

	/s/ Paul Michaels	 	 
	Paul Michaels, Chairman	 	Date
	Curative Biotechnology Holdings, Inc.	 	 

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 22 of 24	Confidential	Revised October 18, 2018

    	 

    

 

CONTACTS
INFORMATION PAGE

 

CRADA
Notices

 

	For
    NEI:	 	For
    Collaborator:
	 	 	 
	Technology
    Transfer Specialist	 	Curative
    Biotechnology Holdings, Inc. 
	National
    Eye Institute	 	1825
    NW Corporate Blvd #110
	9609
    Medical Center Drive	 	Boca
    Raton FL 33431
	Room
    1-E530	 	Email:
    irgarr@curativebiotech.com
	Bethesda,
    MD 20892-9702 MSC 9702	 	Tel:
    (240-475-3148)
	Rockville,
    MD 20850-9702 (express mail)	 	 
	Tel:
    240-276-5530	 	 
	Fax:
    240-276-5504	 	 

 

Patenting
and Licensing

 

	For
    IC:	 	For
    Collaborator (if separate from above)
	 	 	 
	Technology
    Transfer Center	 	Curative
    Biotechnology Holdings, Inc. 
	National
    Cancer Institute	 	1825
    NW Corporate Blvd #110
	9609
    Medical Center Drive	 	Boca
    Raton FL 33431
	Room
    1-E530, MSC 9702	 	Email:
    irgarr@curativebiotech.com
	Rockville,
    MD 20892-9702	 	Tel:
    (240-475-3148)
	Tel:
    240-276-5530	 	 
	Fax:
    240-276-5524	 	 

 

Delivery
of Materials Identified in Appendix B (if any)

 

	For
    IC:	 	For
    Collaborator:
	 	 	 
	National
    Institutes of Health	 	Curative
    Biotechnology Holdings, Inc. 
	10
    Center Drive, MSC 1196, Building 10	 	1825
    NW Corporate Blvd #110
	Bethesda,
    MD 20892-1196	 	Boca
    Raton FL 33431
	Tel:
    301-402-8153	 	Email:
    irgarr@curativebiotech.com 
	Email:	 	Tel:
    (240-475-3148)

 

Finances

 

CRADA
Funds, Budget Officer, NEI

Building
31 - Claude D. Pepper Building, 6A16 31

Center
Dr., MS2510. Bethesda, MD

Phone:
301-496-5243 Fax: 301-402-2870 E-mail: NEIFMB@mail.nih.gov 

Clinical
and Safety Reporting Contacts (as needed for Article 4.4)

 

For
IC:

 

National
Eye Institute

9609
Medical Center Drive, Room 2W330, MSC 9716 Rockville, MD 20850 (for USPS mail)

Bethesda,
MD 20892-9716 (for couriers)

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 23 of 24	Confidential	Revised October 18, 2018

    	 

    

 

SUMMARY
PAGE

 

EITHER
PARTY MAY, WITHOUT FURTHER CONSULTATION OR PERMISSION,

RELEASE
THIS SUMMARY PAGE TO THE PUBLIC.

 

	TITLE
    OF CRADA:	 	Clinical
    Evaluation of Curative Biotechnology Holdings, Inc.’s
    Proprietary Ocular Metformin Formulation
	 	 	 
	PHS
    IC:	 	National
    Eye Institute
	IC
    Principal Investigator:	 	Emily
    Chew, M.D.
	 	 	 
	Collaborator:	 	Curative
    Biotechnology, Inc.
	Collaborator
    Principal Investigator	 	Steering
    committee lead representative Dr. Catherine Sohn 
	 	 	 
	TERM
    OF CRADA:	 	Three
    (3) years from the Effective Date.

 

ABSTRACT
OF THE RESEARCH PLAN:

 

Under
a Cooperative Research and Development Agreement (CRADA), the National Eye Institute and Curative Biotechnology, Inc. (Curative) will
collaborate to evaluate Curative’s proprietary ocular metformin formulation in clinical studies for the treatment of intermediate
and late-stage Age-Related Macular Degeneration (AMD) disease.

 

    	PHS ICT-CRADA	Agreement Ref. No. 03434	MODEL ADOPTED June 18, 2009
	Page 24 of 24	Confidential	Revised October 18, 2018

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