Document:

Exhibit 4.8

 

PUBLIC HEALTH SERVICE

 

PATENT LICENSE AGREEMENT—EXCLUSIVE

 

COVER PAGE

 

For PHS internal use only:

 

	 	Patent License Number:	 	 
	 	 	 	 
	 	L-249-2001/0	 	 
	 	 	 	 
	 	Serial Number(s) of Licensed Patent(s) and/or Patent Application(s):
	 	 	 	 
	 	08/091.109: 08/163,324: 5,773,423	 	 
	 	 	 	 
	 	Licensee:	 	 
	 	 	 	 
	 	Can-Fite BioPharma, Ltd.	 	 
	 	 	 	 
	 	Cooperative Research and Development Agreement (CRADA) Number (if applicable):
	 	 
	 	 	 	 
	 	 	 	 
	 	Additional Remarks:	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	Public Benefit(s):	 	 
	 	 	 	 
	 	 	 	 

 

This Patent License Agreement, hereinafter referred to as the
“Agreement”, consists of this Cover Page, an attached Agreement, a Signature Page, Appendix A (List
of Patent(s) and/or Patent Application(s)), Appendix B (Fields of Use and Territory), Appendix C (Royalties), Appendix D (Modifications),
Appendix E (Benchmarks), and Appendix F (Commercial Development Plan). The Parties to this Agreement are:

 

		1)	The National Institutes of Health (“NIH”), the Centers
                                                            for Disease Control and Prevention (“CDC”), or the Food
                                                            and Drug Administration (“FDA”), hereinafter singly or
                                                            collectively referred to as “PHS”, agencies of
                                                            the United States Public Health Service within the Department of Health
                                                            and Human Services (“DHHS”); and

 

		2)	The person, corporation, or institution identified above and/or
                                                            on the Signature Page, having offices at the address indicated on
                                                            the Signature Page, hereinafter referred to as “Licensee”.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 1 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

PHS PATENT LICENSE AGREEMENT—EXCLUSIVE

 

PHS and Licensee
agree as follows:

 

		1.	BACKGROUND

 

		1.01	In the course of conducting biomedical and behavioral research, PHS investigators made inventions that may have commercial
applicability.

 

		1.02	By assignment of rights from PHS employees and other inventors, DHHS, on behalf of the United States Government,
owns intellectual property rights claimed in any United States and/or foreign patent applications or patents corresponding to the
assigned inventions. DHHS also owns any tangible embodiments of these inventions actually reduced to practice by PHS.

 

		1.03	The Secretary of DHHS has delegated to PHS the
                                                                authority to enter into this Agreement for the licensing
                                                                of rights to these inventions.

 

		1.04	PHS desires to transfer these inventions to the private sector through commercialization licenses to facilitate the
commercial development of products and processes for public use and benefit.

 

		1.05	Licensee desires to acquire commercialization rights to certain of these inventions in order to develop processes, methods,
and/or marketable products for public use and benefit.

 

		2.	DEFINITIONS

 

		2.01	“Benchmarks” mean the performance milestones that are set forth in Appendix E.

 

		2.02	“Commercial Development Plan” means the written commercialization plan attached as Appendix F.

 

		2.03	“First Commercial Sale” means the initial transfer by or on behalf of Licensee or its sublicensees
of Licensed Products or the initial practice of a Licensed Process by or on behalf of Licensee or its sublicensees
in exchange for cash or some equivalent to which value can be assigned for the purpose of determining Net Sales.

 

		2.04	“Government” means the Government of the United States of America.

 

		2.05	“Licensed Fields of Use” means the fields of use identified in Appendix B.

 

		2.06	“Licensed Patent Rights” shall mean:

 

		a)	Patent applications (including provisional patent applications and PCT patent applications) and/or patents listed in Appendix
A, all divisions and continuations of these applications, all patents issuing from such applications, divisions, and continuations,
and any reissues, reexaminations, and extensions of all such patents;

 

		b)	to the extent that the following contain one or more claims directed to the invention or inventions disclosed in a) above:
i) continuations-in-part of a) above; ii) all divisions and continuations of these continuations-in-part; iii) all patents issuing
from such continuations-in-part, divisions, and continuations; iv) priority patent application(s) of a) above; and v) any reissues,
reexaminations, and extensions of all such patents;

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 2 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		c)	to the extent that the following contain one or more claims directed to the invention or inventions disclosed in a) above:
all counterpart foreign and U.S. patent applications and patents to a) and b) above, including those listed in Appendix A.

 

Licensed Patent Rights shall not include
b) or c) above to the extent that they contain one or more claims directed to new matter which is not the subject matter disclosed
in a) above.

 

		2.07	“Licensed Process(es)” means processes which, in the course of being practiced would be within the scope of
one or more claims of the Licensed Patent Rights that have not been held unpatentable, invalid or unenforceable by an unappealed
or unappealable judgment of a court of competent jurisdiction.

 

		2.08	“Licensed Product(s)” means tangible materials which, in the course of manufacture, use, sale, or importation
would be within the scope of one or more claims of the Licensed Patent Rights that have not been held unpatentable, invalid
or unenforceable by an unappealed or unappealable judgment of a court of competent jurisdiction.

 

		2.09	“Licensed Territory” means the geographical area identified in Appendix B.

 

		2.10	“Net Sales” means the total gross receipts
                                                              for sales of Licensed Products or practice of Licensed
                                                              Processes by or on behalf of Licensee or its sublicensees,
                                                              and from leasing, renting, or otherwise making Licensed Products
                                                              available to others without sale or other dispositions, whether
                                                              invoiced or not, less returns and allowances, packing costs, insurance
                                                              costs, freight out, taxes or excise duties imposed on the transaction
                                                              (if separately invoiced), and wholesaler and cash discounts in amounts
                                                              customary in the trade to the extent actually granted. No deductions
                                                              shall be made for commissions paid to individuals, whether they
                                                              be with independent sales agencies or regularly employed by Licensee,
                                                              or sublicensees, and on its payroll, or for the cost of collections.

 

		2.11	“Practical Application” means to manufacture in the case of a composition or product, to practice in the case
of a process or method, or to operate in the case of a machine or system; and in each case, under such conditions as to establish
that the invention is being utilized and that its benefits are to the extent permitted by law or Government regulations
available to the public on reasonable terms.

 

		2.12	“Research License” means a nontransferable,
                                                              nonexclusive license to make and to use the Licensed Products
                                                              or Licensed Processes as defined by the Licensed Patent
                                                              Rights for purposes of research and not for purposes of commercial
                                                              manufacture or distribution or in lieu of purchase.

 

		3	GRANT OF RIGHTS

 

		3.01	PHS hereby grants and Licensee accepts, subject
                                                              to the terms and conditions of this Agreement, an exclusive
                                                              license under the Licensed Patent Rights in the Licensed
                                                              Territory to make and have made, to use and have used, to sell
                                                              and have sold, to offer to sell, and to import any Licensed Products
                                                              in the Licensed Fields of Use and to practice and have
                                                              practiced any Licensed Processes in the Licensed Fields
                                                              of Use.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 3 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		3.02	This Agreement confers no license or rights by implication,
                                                                estoppel, or otherwise under any patent applications or patents
                                                                of PHS other than Licensed Patent Rights regardless
                                                                of whether such patents are dominant or subordinate to Licensed
                                                                Patent Rights.

 

		4.	SUBLICENSING

 

		4.01	Upon written approval by PHS, which approval will not be unreasonably withheld, Licensee may enter into sublicensing
agreements under the Licensed Patent Rights.

 

		4.02	Licensee agrees that any sublicenses granted by it
                                                                shall provide that the obligations to PHS of Paragraphs
                                                                5.01-5.04, 8.01, 10.01, 10.02, 12.05, and 13.07-13.09 of this
                                                                Agreement shall be binding upon the sublicensee as if it
                                                                were a party to this Agreement. Licensee further
                                                                agrees to attach copies of these Paragraphs to all sublicense
                                                                agreements.

 

		4.03	Any sublicensee granted by Licensee shall provide for the termination of the sublicense, or the conversion to a license
directly between such sublicensees and PHS, at the option of the sublicensee, upon termination of this Agreement
under Article 13. Such conversion is subject to PHS approval and contingent upon acceptance by the sublicensee of the remaining
provisions of this Agreement.

 

		4.04	Licensee agrees to forward to PHS a copy of each fully executed sublicense agreement postmarked within thirty
(30) days of the execution of such agreement. To the extent permitted law, PHS agrees to maintain each such sublicense agreement
in confidence.

 

		5.	STATUTORY AND PHS REQUIREMENTS AND RESERVED GOVERNMENT
RIGHTS

 

	 	5.01	(a)	PHS reserves
on behalf of the Government an irrevocable, nonexclusive, nontransferable, royalty-free license for the practice of all inventions
licensed under the Licensed Patent Rights throughout the world by or on behalf of the Government and on behalf of any foreign
government or international organization pursuant to any existing or future treaty or agreement to which the Government is a signatory.
Prior to the First Commercial Sale, Licensee agrees to provide PHS reasonable quantities of Licensed Products
or materials made through the Licensed Processes for PHS research use.

 

		(b)	In the event that Licensed Patent Rights are Subject Inventions
                                                             made under a Cooperative Research and Development Agreement (CRADA),
                                                             Licensee grants to the Government, pursuant to 15 U.S.C. 3710a(b)(l)(A),
                                                             a nonexclusive, nontransferable, irrevocable, paid-up license to
                                                             practice Licensed Patent Rights or have Licensed Patent
                                                             Rights practiced throughout the world by or on behalf of the
                                                             Government. In the exercise of such license, the Government shall
                                                             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 as such if it had been obtained
                                                             from a non-Federal party. Prior to the First Commercial Sale,
                                                             Licensee agrees to provide PHS reasonable quantities of
                                                             Licensed Products or materials made through the Licensed
                                                             Processes for PHS research use.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 4 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		5.02	Licensee agrees that products used or sold in the United States embodying Licensed Products or produced through
use of Licensed Processes shall be manufactured substantially in the United States, unless a written waiver is obtained
in advance from PHS.

 

		5.03	Licensee acknowledges that PHS may enter into
                                                              future Cooperative Research and Development Agreements (CRADAs)
                                                              under the Federal Technology Transfer Act of 1986 that relate to
                                                              the subject matter of this Agreement. Licensee agrees
                                                              not to unreasonably deny requests for a Research License
                                                              from such future collaborators with PHS when acquiring such
                                                              rights is necessary in order to make a Cooperative Research and
                                                              Development Agreement (CRADA) project feasible. Licensee
                                                              may request an opportunity to join as a party to the proposed Cooperative
                                                              Research and Development Agreement (CRADA).

 

		5.04	(a)	In addition to the reserved license of Paragraph 5.01
above, PHS reserves the right to grant nonexclusive Research Licenses directly or to require Licensee to grant nonexclusive
Research Licenses on reasonable terms. The purpose of this Research License is to encourage basic research, whether conducted
at an academic or corporate facility. In order to safeguard the Licensed Patent Rights, however, PHS shall consult
with Licensee before granting to commercial entities a Research License or providing to them research samples of materials
made through the Licensed Processes.

 

		(b)	In exceptional
                                                                               circumstances, and in the event that Licensed
                                                                               Patent Rights are Subject Inventions made under
                                                                               a Cooperative Research and Development Agreement
                                                                               (CRADA), the Government, pursuant to 15 U.S.C.
                                                                               3710a(b)(1)(B), retains the right to require the
                                                                               Licensee to grant to a responsible applicant
                                                                               a nonexclusive, partially exclusive, or exclusive
                                                                               sublicense to use Licensed Patent Rights
                                                                               in Licensee’s field of use on terms
                                                                               that are reasonable under the circumstances; or
                                                                               if Licensee fails to grant such a license,
                                                                               the Government retains the right to grant the license
                                                                               itself. The exercise of such rights by the Government
                                                                               shall 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 Licensee;
                                                                               (ii) the action is necessary to meet requirements
                                                                               for public use specified by Federal regulations,
                                                                               and such requirements are not reasonably satisfied
                                                                               by the Licensee; or (iii) the Licensee
                                                                               has failed to comply with an agreement containing
                                                                               provisions described in 15 U.S.C. 37l0a(c)(4)(B).
                                                                               The determination made by the Government under
                                                                               this Article is subject to administrative appeal
                                                                               and judicial review under 35 U.S.C. 203(2).

 

		6.	ROYALTIES AND
                                                                               REIMBURSEMENT

 

		6.01	Licensee agrees to pay to PHS a noncreditable, nonrefundable license issue royalty as set forth in Appendix C
within thirty (30) days from the date that this Agreement becomes effective.

 

		6.02	Licensee agrees to pay to PHS a nonrefundable
                                                              minimum annual royalty as set forth in Appendix C. The minimum annual
                                                              royalty is due and payable on January 1 of each calendar year and
                                                              may be credited against any earned royalties due for sales made
                                                              in that year. The minimum annual royalty for the first calendar
                                                              year of this Agreement is due and payable within thirty
                                                              (30) days of execution of this license and may be prorated according
                                                              to the fraction of the calendar year remaining between the effective
                                                              date of this Agreement and the next subsequent January 1.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 5 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		6.03	Licensee
                                                                                                    agrees to pay PHS
                                                                                                    earned royalties as set forth
                                                                                                    in Appendix C.

 

		6.04	Licensee
                                                                                                    agrees to pay PHS
                                                                                                    benchmark royalties as set
                                                                                                    forth in Appendix C.

 

		6.05	Licensee
                                                                                                    agrees to pay PHS
                                                                                                    sublicensing royalties as
                                                                                                    set forth in Appendix C.

 

		6.06	A
                                                                                                    patent or patent application
                                                                                                    licensed under this Agreement
                                                                                                    shall cease to fall within
                                                                                                    the Licensed Patent Rights
                                                                                                    for the purpose of computing
                                                                                                    earned royalty payments in
                                                                                                    any given country on the earliest
                                                                                                    of the dates that a) the application
                                                                                                    has been abandoned and not
                                                                                                    continued, b) the patent expires
                                                                                                    or irrevocably lapses, or
                                                                                                    c) the claim has been held
                                                                                                    to be invalid or unenforceable
                                                                                                    by an unappealed or unappealable
                                                                                                    decision of a court of competent
                                                                                                    jurisdiction or administrative
                                                                                                    agency.

 

		6.07	No
                                                                                                    multiple royalties shall be
                                                                                                    payable because any Licensed
                                                                                                    Products or Licensed
                                                                                                    Processes are covered
                                                                                                    by more than one of the Licensed
                                                                                                    Patent Rights.

 

		6.08	On
                                                                                                    sales of Licensed Products
                                                                                                    by Licensee to
                                                                                                    sublicensees or on sales made
                                                                                                    in other than an arm’s
                                                                                                    -length transaction, the value
                                                                                                    of the Net Sales attributed
                                                                                                    under this Article 6 to such
                                                                                                    a transaction shall be that
                                                                                                    which would have been received
                                                                                                    in an arm’s-length transaction,
                                                                                                    based on sales of like quantity
                                                                                                    and quality products on or
                                                                                                    about the time of such transaction.

 

		6.09	With
                                                                                                    regard to expenses associated
                                                                                                    with the preparation, filing,
                                                                                                    prosecution, and maintenance
                                                                                                    of all patent applications
                                                                                                    and patents included within
                                                                                                    the Licensed Patent Rights
                                                                                                    incurred by PHS
                                                                                                    prior to the effective date
                                                                                                    of this Agreement,
                                                                                                    Licensee shall pay
                                                                                                    to PHS, as an additional
                                                                                                    royalty, within sixty (60)
                                                                                                    days of PHS’s
                                                                                                    submission of a statement
                                                                                                    and request for payment to
                                                                                                    Licensee, an amount
                                                                                                    equivalent to such patent
                                                                                                    expenses previously incurred
                                                                                                    by PHS.

 

		6.10	With
                                                                                                    regard to expenses associated
                                                                                                    with the preparation, filing,
                                                                                                    prosecution, and maintenance
                                                                                                    of all patent applications
                                                                                                    and patents included within
                                                                                                    the Licensed Patent Rights
                                                                                                    incurred by PHS
                                                                                                    on or after the effective
                                                                                                    date of this Agreement,
                                                                                                    PHS, at its sole option,
                                                                                                    may require Licensee:

 

(a) to pay PHS on an annual
basis, within sixty (60) days of PHS’s submission of a statement and request for payment, a royalty amount equivalent
to all such patent expenses incurred during the previous calendar year(s); or

 

(b) to pay such expenses directly
to the law firm employed by PHS to handle such functions. However, in such event, PHS and not Licensee shall
be the client of such law firm.

 

In limited circumstances, Licensee may
be given the right to assume responsibility for the preparation, filing, prosecution, or maintenance of any patent
application or patent included with the Licensed Patent Rights.  In that event, Licensee shall directly pay the
attorneys or agents engaged to prepare, file, prosecute, or maintain such patent applications or patents and shall provide to PHS
copies of each invoice associated with such services as well as documentation that such invoices have been paid.

 

		6.11	Licensee
                                                                                                    may elect to surrender
                                                                                                    its rights in any country
                                                                                                    of the Licensed Territory
                                                                                                    under any Licensed
                                                                                                    Patent Rights upon ninety
                                                                                                    (90) days written notice to
                                                                                                    PHS and owe no payment
                                                                                                    obligation under Article 6.10
                                                                                                    for patent-related expenses
                                                                                                    incurred in that country after
                                                                                                    ninety (90) days of the effective
                                                                                                    date of such written notice.

 

CONFIDENTIAL
PHS Patent License Agreement—Exclusive L-249-01/0 with CanFite

Model 980611a Page 6 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		7.	PATENT FILING, PROSECUTION, AND MAINTENANCE

 

		7.01	Except
                                                                                                    as otherwise provided in this
                                                                                                    Article 7, PHS agrees
                                                                                                    to take responsibility for,
                                                                                                    but to consult with, the Licensee
                                                                                                    in the preparation, filing,
                                                                                                    prosecution, and maintenance
                                                                                                    of any and all patent applications
                                                                                                    or patents included in the
                                                                                                    Licensed Patent Rights
                                                                                                    and shall furnish copies
                                                                                                    of relevant patent-related
                                                                                                    documents to Licensee.

 

		7.02	Upon
                                                                                                    PHS’s written
                                                                                                    request, Licensee shall
                                                                                                    assume the responsibility
                                                                                                    for the preparation, filing,
                                                                                                    prosecution, and maintenance
                                                                                                    of any and all patent applications
                                                                                                    or patents included in the
                                                                                                    Licensed Patent Rights
                                                                                                    and shall on an ongoing
                                                                                                    basis promptly furnish copies
                                                                                                    of all patent-related documents
                                                                                                    to PHS. In such event,
                                                                                                    Licensee shall, subject
                                                                                                    to the prior approval of PHS,
                                                                                                    select registered patent attorneys
                                                                                                    or patent agents to provide
                                                                                                    such services on behalf of
                                                                                                    Licensee and PHS.
                                                                                                    PHS shall provide appropriate
                                                                                                    powers of attorney and other
                                                                                                    documents necessary to undertake
                                                                                                    such actions to the patent
                                                                                                    attorneys or patent agents
                                                                                                    providing such services. Licensee
                                                                                                    and its attorneys or agents
                                                                                                    shall consult with PHS
                                                                                                    in all aspects of the
                                                                                                    preparation, filing, prosecution
                                                                                                    and maintenance of patent
                                                                                                    applications and patents included
                                                                                                    within the Licensed Patent
                                                                                                    Rights and shall provide
                                                                                                    PHS sufficient opportunity
                                                                                                    to comment on any document
                                                                                                    that Licensee intends
                                                                                                    to file or to cause to be
                                                                                                    filed with the relevant intellectual
                                                                                                    property or patent office.

 

		7.03	At
                                                                                                    any time, PHS may provide
                                                                                                    Licensee with written
                                                                                                    notice that PHS wishes
                                                                                                    to assume control of the preparation,
                                                                                                    filing, prosecution, and maintenance
                                                                                                    of any and all patent applications
                                                                                                    or patents included in the
                                                                                                    Licensed Patent Rights.
                                                                                                    If PHS elects to assume
                                                                                                    such responsibilities, Licensee
                                                                                                    agrees to cooperate fully
                                                                                                    with PHS, its attorneys,
                                                                                                    and agents in the preparation,
                                                                                                    filing, prosecution, and maintenance
                                                                                                    of any and all patent applications
                                                                                                    or patents included in the
                                                                                                    Licensed Patent Rights
                                                                                                    and to provide PHS
                                                                                                    with complete copies of
                                                                                                    any and all documents or other
                                                                                                    materials that PHS
                                                                                                    deems necessary to undertake
                                                                                                    such responsibilities. Licensee
                                                                                                    shall be responsible for
                                                                                                    all costs associated with
                                                                                                    transferring patent prosecution
                                                                                                    responsibilities to an attorney
                                                                                                    or agent of PHS’s
                                                                                                    choice.

 

		7.04	Each
                                                                                                    party shall promptly inform
                                                                                                    the other as to all matters
                                                                                                    that come to its attention
                                                                                                    that may affect the preparation,
                                                                                                    filing, prosecution, or maintenance
                                                                                                    of the Licensed Patent
                                                                                                    Rights and permit each
                                                                                                    other to provide comments
                                                                                                    and suggestions with respect
                                                                                                    to the preparation, Filing,
                                                                                                    prosecution, and maintenance
                                                                                                    of Licensed Patent Rights,
                                                                                                    which comments and suggestions
                                                                                                    shall be considered by the
                                                                                                    other party.

 

		8.	RECORD KEEPING

 

		8.01	Licensee
                                                                                                    agrees to keep accurate
                                                                                                    and correct records of Licensed
                                                                                                    Products made, used, sold,
                                                                                                    or imported and Licensed
                                                                                                    Processes practiced under
                                                                                                    this Agreement appropriate
                                                                                                    to determine the amount of
                                                                                                    royalties due PHS.
                                                                                                    Such records shall be retained
                                                                                                    for at least five (5) years
                                                                                                    following a given reporting
                                                                                                    period and shall be available
                                                                                                    during normal business hours
                                                                                                    for inspection at the expense
                                                                                                    of PHS by an accountant
                                                                                                    or other designated auditor
                                                                                                    selected by PHS for
                                                                                                    the sole purpose of verifying
                                                                                                    reports and payments hereunder.
                                                                                                    The accountant or auditor
                                                                                                    shall only disclose to PHS
                                                                                                    information relating to
                                                                                                    the accuracy of reports and
                                                                                                    payments made under this Agreement.
                                                                                                    If an inspection shows an
                                                                                                    underreporting or underpayment
                                                                                                    in excess of five percent
                                                                                                    (5%) for any twelve (12) month
                                                                                                    period, then Licensee
                                                                                                    shall reimburse PHS
                                                                                                    for the cost of the inspection
                                                                                                    at the time Licensee
                                                                                                    pays the unreported royalties,
                                                                                                    including any late charges
                                                                                                    as required by Paragraph 9.08
                                                                                                    of this Agreement.
                                                                                                    All payments required under
                                                                                                    this Paragraph shall be due
                                                                                                    within thirty (30) days of
                                                                                                    the date PHS provides
                                                                                                    Licensee notice of
                                                                                                    the payment due.

 

CONFIDENTIAL
PHS Patent License Agreement—Exclusive L-249-01/0 with CanFite

Model 980611a Page 7 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		8.02	Licensee
                                                                                                    agrees to have an audit
                                                                                                    of sales and royalties conducted
                                                                                                    by an independent auditor
                                                                                                    at least every two (2) years
                                                                                                    if annual sales of the Licensed
                                                                                                    Product or Licensed
                                                                                                    Processes are over two
                                                                                                    (2) million dollars. The audit
                                                                                                    shall address, at a minimum,
                                                                                                    the amount of gross sales
                                                                                                    by or on behalf of Licensee
                                                                                                    during the audit period,
                                                                                                    terms of the license as to
                                                                                                    percentage or fixed royalty
                                                                                                    to be remitted to the Government,
                                                                                                    the amount of royalty
                                                                                                    funds owed to the Government
                                                                                                    under this Agreement,
                                                                                                    and whether the royalty
                                                                                                    amount owed has been paid
                                                                                                    to the Government and
                                                                                                    is reflected in the records
                                                                                                    of the Licensee. The
                                                                                                    audit shall also indicate
                                                                                                    the PHS license number,
                                                                                                    product, and the time period
                                                                                                    being audited. A report certified
                                                                                                    by the auditor shall be submitted
                                                                                                    promptly by the auditor directly
                                                                                                    to PHS on completion.
                                                                                                    Licensee shall pay
                                                                                                    for the entire cost of the
                                                                                                    audit.

 

		9	REPORTS ON PROGRESS, BENCHMARKS, SALES, AND PAYMENTS

 

		9.01	Prior
                                                                                                    to signing this Agreement,
                                                                                                    Licensee has provided
                                                                                                    to PHS the Commercial
                                                                                                    Development Plan at Appendix
                                                                                                    F, under which Licensee
                                                                                                    intends to bring the subject
                                                                                                    matter of the Licensed
                                                                                                    Patent Rights to the point
                                                                                                    of Practical Application.
                                                                                                    This Commercial Development
                                                                                                    Plan is hereby incorporated
                                                                                                    by reference into this Agreement.
                                                                                                    Based on this plan, performance
                                                                                                    Benchmarks are determined
                                                                                                    as specified in Appendix E.

 

		9.02	Licensee
                                                                                                    shall provide written
                                                                                                    annual reports on its product
                                                                                                    development progress or efforts
                                                                                                    to commercialize under the
                                                                                                    Commercial Development
                                                                                                    Plan for each of the Licensed
                                                                                                    Fields of Use within sixty
                                                                                                    (60) days after December 31
                                                                                                    of each calendar year. These
                                                                                                    progress reports shall include,
                                                                                                    but not be limited to; progress
                                                                                                    on research and development,
                                                                                                    status of applications for
                                                                                                    regulatory approvals, manufacturing,
                                                                                                    sublicensing, marketing, importing,
                                                                                                    and sales during the preceding
                                                                                                    calendar year, as well as
                                                                                                    plans for the present calendar
                                                                                                    year. PHS also encourages
                                                                                                    these reports to include information
                                                                                                    on any of Licensee’s
                                                                                                    public service activities
                                                                                                    that relate to the Licensed
                                                                                                    Patent Rights. If reported
                                                                                                    progress differs from that
                                                                                                    projected in the Commercial
                                                                                                    Development Plan and
                                                                                                    Benchmarks, Licensee shall
                                                                                                    explain the reasons for such
                                                                                                    differences. In any such annual
                                                                                                    report, Licensee may
                                                                                                    propose amendments to the
                                                                                                    Commercial Development
                                                                                                    Plan, acceptance of which
                                                                                                    by PHS may not be denied
                                                                                                    unreasonably. Licensee
                                                                                                    agrees to provide any
                                                                                                    additional information reasonably
                                                                                                    required by PHS to
                                                                                                    evaluate Licensee’s
                                                                                                    performance under this
                                                                                                    Agreement. Licensee
                                                                                                    may amend the Benchmarks
                                                                                                    at any time upon written consent
                                                                                                    by PHS. PHS
                                                                                                    shall not unreasonably withhold
                                                                                                    approval of any request of
                                                                                                    Licensee to extend
                                                                                                    the time periods of this schedule
                                                                                                    if such request is supported
                                                                                                    by a reasonable showing by
                                                                                                    Licensee of diligence
                                                                                                    in its performance under the
                                                                                                    Commercial Development
                                                                                                    Plan and toward bringing
                                                                                                    the Licensed Products to
                                                                                                    the point of Practical
                                                                                                    Application as defined
                                                                                                    in 37 CFR 404.3(d). Licensee
                                                                                                    shall amend the Commercial
                                                                                                    Development Plan and Benchmarks
                                                                                                    at the request of PHS
                                                                                                    to address any Licensed
                                                                                                    Fields of Use not specifically
                                                                                                    addressed in the plan originally
                                                                                                    submitted.

 

		9.03	Licensee
                                                                                                    shall report to PHS
                                                                                                    the dates for achieving
                                                                                                    Benchmarks specified
                                                                                                    in Appendix E and the First
                                                                                                    Commercial Sale in each
                                                                                                    country in the Licensed
                                                                                                    Territory within thirty
                                                                                                    (30) days of such occurrences.

 

		9.04	Licensee
                                                                                                    shall submit to PHS
                                                                                                    within sixty (60) days
                                                                                                    after each calendar half-year
                                                                                                    ending June 30 and December
                                                                                                    31 a royalty report setting
                                                                                                    forth for the preceding half-year
                                                                                                    period the amount of the Licensed
                                                                                                    Products sold or Licensed
                                                                                                    Processes practiced by
                                                                                                    or on behalf of Licensee
                                                                                                    in each country within
                                                                                                    the Licensed Territory,
                                                                                                    the Net Sales,
                                                                                                    and the amount of royalty
                                                                                                    accordingly due. With each
                                                                                                    such royalty report, Licensee
                                                                                                    shall submit payment of
                                                                                                    the earned royalties due,
                                                                                                    If no earned royalties are
                                                                                                    due to PHS for any
                                                                                                    reporting period, the written
                                                                                                    report shall so state. The
                                                                                                    royalty report shall be certified
                                                                                                    as correct by an authorized
                                                                                                    officer of Licensee
                                                                                                    and shall include a detailed
                                                                                                    listing of all deductions
                                                                                                    made under Paragraph 2.10
                                                                                                    to determine Net Sales
                                                                                                    made under Article 6 to
                                                                                                    determine royalties due.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 8  of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		9.05	Licensee
                                                                                                    agrees to forward semi-annually
                                                                                                    to PHS a copy of such
                                                                                                    reports received by Licensee
                                                                                                    from its sublicensees
                                                                                                    during the preceding half-year
                                                                                                    period as shall be pertinent
                                                                                                    to a royalty accounting to
                                                                                                    PHS by Licensee
                                                                                                    for activities under the
                                                                                                    sublicense.

 

		9.06	Royalties
                                                                                                    due under Article 6 shall
                                                                                                    be paid in U.S. dollars. For
                                                                                                    conversion of foreign currency
                                                                                                    to U.S. dollars, the conversion
                                                                                                    rate shall be the New York
                                                                                                    foreign exchange rate quoted
                                                                                                    in The Wall Street Journal
                                                                                                    on the day that the payment
                                                                                                    is due. All checks and bank
                                                                                                    drafts shall be drawn on United
                                                                                                    States banks and shall be
                                                                                                    payable, as appropriate, to
                                                                                                    “NIH/Patent Licensing.”
                                                                                                    All such payments shall be
                                                                                                    sent to the following address:
                                                                                                    NIH, P.O. Box 360120, Pittsburgh,
                                                                                                    PA 15251-6120. Any loss of
                                                                                                    exchange, value, taxes, or
                                                                                                    other expenses incurred in
                                                                                                    the transfer or conversion
                                                                                                    to U.S. dollars shall be paid
                                                                                                    entirely by Licensee.
                                                                                                    The royalty report required
                                                                                                    by Paragraph 9.04 of this
                                                                                                    Agreement shall accompany
                                                                                                    each such payment, and a copy
                                                                                                    of such report shall also
                                                                                                    be mailed to PHS at
                                                                                                    its address for notices indicated
                                                                                                    on the Signature Page of this
                                                                                                    Agreement.

 

		9.07	Licensee
                                                                                                    shall be solely responsible
                                                                                                    for determining if any tax
                                                                                                    on royalty income is owed
                                                                                                    outside the United States
                                                                                                    and shall pay any such tax
                                                                                                    and be responsible for all
                                                                                                    filings with appropriate agencies
                                                                                                    of foreign governments,

 

		9.08	Interest
                                                                                                    and penalties may be assessed
                                                                                                    by PHS on any overdue
                                                                                                    payments in accordance with
                                                                                                    the Federal Debt Collection
                                                                                                    Act. The payment of such late
                                                                                                    charges shall not prevent
                                                                                                    PHS from exercising
                                                                                                    any other rights it may have
                                                                                                    as a consequence of the lateness
                                                                                                    of any payment.

 

		9.09	All
                                                                                                    plans and reports required
                                                                                                    by this Article 9 and marked
                                                                                                    “confidential” by
                                                                                                    Licensee shall, to
                                                                                                    the extent permitted by law,
                                                                                                    be treated by PHS as
                                                                                                    commercial and financial information
                                                                                                    obtained from a person and
                                                                                                    as privileged and confidential,
                                                                                                    and any proposed disclosure
                                                                                                    of such records by the PHS
                                                                                                    under the Freedom of Information
                                                                                                    Act (FOIA), 5 U.S.C. §552 shall
                                                                                                    be subject to the predisclosure
                                                                                                    notification requirements
                                                                                                    of 45 CFR §5.65(d).

 

		9.10	Licensee
                                                                                                    shall submit to PHS
                                                                                                    a satisfactory clinical
                                                                                                    research and development plan
                                                                                                    for the non- prime indications
                                                                                                    listed in Appendix B within
                                                                                                    six (6) months from the date
                                                                                                    that this Agreement
                                                                                                    becomes effective. That development
                                                                                                    plan will include new Appendix
                                                                                                    E performance benchmarks and
                                                                                                    updating of the Appendix F
                                                                                                    Commercial Development Plan
                                                                                                    as necessary to encompass
                                                                                                    the clinical development of
                                                                                                    the non-prime indications.
                                                                                                    PHS will notify Licensee
                                                                                                    in writing as to whether
                                                                                                    the development plan submitted
                                                                                                    is satisfactory. If PHS
                                                                                                    determines the clinical
                                                                                                    research and development plan
                                                                                                    submitted by Licensee
                                                                                                    to be unsatisfactory, Licensee
                                                                                                    will be notified in writing
                                                                                                    of any deficiencies and Licensee
                                                                                                    will be provided with
                                                                                                    an additional ninety (90)
                                                                                                    days to remedy the deficiencies.
                                                                                                    Acceptance of said clinical
                                                                                                    research and development program
                                                                                                    for the non-prime indications
                                                                                                    shall not be unreasonably
                                                                                                    withheld and which shall take
                                                                                                    into account Licensee’s
                                                                                                    ongoing efforts and normal
                                                                                                    drag development standards
                                                                                                    for obtaining FDA approval
                                                                                                    for multiple indication prophylactic
                                                                                                    and therapeutic products.
                                                                                                    If PHS reasonably determines
                                                                                                    that Licensee did not
                                                                                                    submit a satisfactory development
                                                                                                    plan during the ninety day
                                                                                                    period, PHS may withdraw
                                                                                                    the non-prime indications
                                                                                                    from the Appendix B Licensed
                                                                                                    Fields of Use upon written
                                                                                                    notification to the Licensee.
                                                                                                    Licensee agrees that withdrawal
                                                                                                    under this Paragraph of the
                                                                                                    non-prime indications is not
                                                                                                    subject to further remedies
                                                                                                    under Article 13. Withdrawal
                                                                                                    of the non-prime indications
                                                                                                    under this Paragraph by PHS
                                                                                                    shall not affect Licensee
                                                                                                    rights under the Licensed
                                                                                                    Patent Rights for the
                                                                                                    Appendix B prime Licensed
                                                                                                    Fields of Use indications.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 9 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		9.11	Licensee
                                                                                                    agrees to use reasonable
                                                                                                    efforts to provide (itself
                                                                                                    or through a sublicensee)
                                                                                                    education programs and materials
                                                                                                    to the United States public
                                                                                                    with respect to the indications
                                                                                                    listed in the Licensed
                                                                                                    Fields of Use. Furthermore,
                                                                                                    following regulatory approval
                                                                                                    for marketing Licensed
                                                                                                    Products in the United
                                                                                                    States, Licensee agrees
                                                                                                    to establish or provide through
                                                                                                    a sublicensee an indigent
                                                                                                    patient access program for
                                                                                                    Licensed Products (or
                                                                                                    to include Licensed Products
                                                                                                    in an existing indigent
                                                                                                    patient access program), in
                                                                                                    accordance with customary
                                                                                                    and standard industry practice,
                                                                                                    such that reasonable quantities
                                                                                                    of Licensed Products
                                                                                                    may be provided to qualified
                                                                                                    indigent citizens of the United
                                                                                                    States who are not covered
                                                                                                    under any public or private
                                                                                                    health plan. Licensee
                                                                                                    further agrees, following
                                                                                                    regulatory approval for marketing
                                                                                                    Licensed Products in
                                                                                                    the United States, and as
                                                                                                    part of its marketing and
                                                                                                    product promotion, to develop
                                                                                                    (itself or through a sublicensee)
                                                                                                    written educational materials
                                                                                                    (including, for example brochures
                                                                                                    and advertisements) directed
                                                                                                    to patients and physicians
                                                                                                    detailing the Licensed
                                                                                                    Products and therapeutic
                                                                                                    uses thereof.

 

		10	PERFORMANCE

 

		10.01	Licensee
                                                                                                     shall use its reasonable
                                                                                                     best efforts to bring the
                                                                                                     Licensed Products
                                                                                                     and Licensed Processes
                                                                                                     to Practical Application.
                                                                                                     “Reasonable best
                                                                                                     efforts” for the purposes
                                                                                                     of this provision shall include
                                                                                                     adherence to the Commercial
                                                                                                     Development Plan
                                                                                                     at Appendix F and performance
                                                                                                     of the Benchmarks
                                                                                                     at Appendix E. The efforts
                                                                                                     of a sublicensee shall be
                                                                                                     considered the efforts of
                                                                                                     Licensee.

 

		10.02	Upon
                                                                                                     the First Commercial Sale,
                                                                                                     until the expiration
                                                                                                     of this Agreement, Licensee
                                                                                                     shall use its reasonable
                                                                                                     best efforts to make Licensed
                                                                                                     Products and Licensed
                                                                                                     Processes reasonably
                                                                                                     accessible to the United
                                                                                                     States public.

 

		11.	INFRINGEMENT AND PATENT ENFORCEMENT

 

		11.01	PHS
                                                                                                     and Licensee agree
                                                                                                     to notify each other promptly
                                                                                                     of each infringement or possible
                                                                                                     infringement of the Licensed
                                                                                                     Patent Rights, as well
                                                                                                     as any facts which may affect
                                                                                                     the validity, scope, or enforceability
                                                                                                     of the Licensed Patent
                                                                                                     Rights of which either
                                                                                                     Party becomes aware.

 

		11.02	Pursuant
                                                                                                     to this Agreement
                                                                                                     and the provisions of Chapter
                                                                                                     29 of title 35, United States
                                                                                                     Code, Licensee may:
                                                                                                     a) bring suit in its own
                                                                                                     name, at its own expense,
                                                                                                     and on its own behalf for
                                                                                                     infringement of presumably
                                                                                                     valid claims in the Licensed
                                                                                                     Patent Rights; b) in
                                                                                                     any such suit, enjoin infringement
                                                                                                     and collect for its use,
                                                                                                     damages, profits, and awards
                                                                                                     of whatever nature recoverable
                                                                                                     for such infringement; and
                                                                                                     c) settle any claim or suit
                                                                                                     for infringement of the Licensed
                                                                                                     Patent Rights provided,
                                                                                                     however, that PHS
                                                                                                     and appropriate Government
                                                                                                     authorities shall have
                                                                                                     the first right to take such
                                                                                                     actions. If Licensee
                                                                                                     desires to initiate a suit
                                                                                                     for patent infringement,
                                                                                                     Licensee shall notify
                                                                                                     PHS in writing. If
                                                                                                     PHS does not notify
                                                                                                     Licensee of its intent
                                                                                                     to pursue legal action within
                                                                                                     ninety (90) days, Licensee
                                                                                                     will be free to initiate
                                                                                                     suit. PHS shall have
                                                                                                     a continuing right to intervene
                                                                                                     in such suit. Licensee
                                                                                                     shall take no action
                                                                                                     to compel the Government
                                                                                                     either to initiate or
                                                                                                     to join in any such suit
                                                                                                     for patent infringement.
                                                                                                     Licensee may request
                                                                                                     the Government to
                                                                                                     initiate or join in any such
                                                                                                     suit if necessary to avoid
                                                                                                     dismissal of the suit. Should
                                                                                                     the Government be
                                                                                                     made a party to any such
                                                                                                     suit, Licensee shall
                                                                                                     reimburse the Government
                                                                                                     for any costs, expenses,
                                                                                                     or fees which the Government
                                                                                                     incurs as a result of
                                                                                                     such motion or other action,
                                                                                                     including any and all costs
                                                                                                     incurred by the Government
                                                                                                     in opposing any such
                                                                                                     motion or other action. In
                                                                                                     all cases, Licensee
                                                                                                     agrees to keep PHS
                                                                                                     reasonably apprised of the
                                                                                                     status and progress of any
                                                                                                     litigation. Before Licensee
                                                                                                     commences an infringement
                                                                                                     action, Licensee shall
                                                                                                     notify PHS and give
                                                                                                     careful consideration to
                                                                                                     the views of PHS and
                                                                                                     to any potential effects
                                                                                                     of the litigation on the
                                                                                                     public health in deciding
                                                                                                     whether to bring suit.

 

CONFIDENTIAL PHS Patent License
Agreement—Exclusive L-249-01/0 with CanFite

Model 980611a Page 10 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

 

		11.03	In the event that a declaratory judgment action alleging
                                                                 invalidity or non-infringement of any of the Licensed Patent
                                                                 Rights shall be brought against Licensee or raised
                                                                 by way of counterclaim or affirmative defense in an infringement
                                                                 suit brought by Licensee under Paragraph 11.02, pursuant
                                                                 to this Agreement and the provisions of Chapter 29 of
                                                                 Title 35, United States Code or other statutes, Licensee
                                                                 may: a) defend the suit in its own name, at its own expense,
                                                                 and on its own behalf for presumably valid claims in the Licensed
                                                                 Patent Rights; b) in any such suit, ultimately to enjoin
                                                                 infringement and to collect for its use, damages, profits, and
                                                                 awards of whatever nature recoverable for such infringement;
                                                                 and c) settle any claim or suit for declaratory judgment involving
                                                                 the Licensed Patent Rights-provided, however, that
                                                                 PHS and appropriate Government authorities shall
                                                                 have the first right to take such actions and shall have a continuing
                                                                 right to intervene in such suit. If PHS does not notify
                                                                 Licensee of its intent to respond to the legal action
                                                                 within a reasonable time, Licensee will be free to do
                                                                 so. Licensee shall take no action to compel the Government
                                                                 either to initiate or to join in any such declaratory judgment
                                                                 action. Licensee may request the Government to
                                                                 initiate or to join any such suit if necessary to avoid dismissal
                                                                 of the suit. Should the Government be made a party to
                                                                 any such suit by motion or any other, action of Licensee,
                                                                 Licensee shall reimburse the Government for any costs,
                                                                 expenses, or fees which the Government incurs as a result
                                                                 of such motion or other action. If Licensee elects not
                                                                 to defend against such declaratory judgment action, PHS,
                                                                 at its option, may do so at its own expense. In all cases, Licensee
                                                                 agrees to keep PHS reasonably apprised of the status
                                                                 and progress of any litigation. Before Licensee commences
                                                                 an infringement action. Licensee shall notify PHS
                                                                 and give careful consideration to the views of PHS and
                                                                 to any potential effects of the litigation on the public health
                                                                 in deciding whether to bring suit.

 

		11.04	In any action under Paragraphs 11.02 or 11.03, the expenses
                                                                 including costs, fees, attorney fees, and disbursements (Action-related
                                                                 Expenses) shall be paid by Licensee. The value of
                                                                 any recovery less Action-elated Expenses made by
                                                                 Licensee through court judgment or settlement shall be
                                                                 treated as Net Sales and subject to earned royalties.

 

		11.05	PHS shall cooperate fully with Licensee in
                                                                 connection with any action under Paragraphs 11.02 or 11.03. PHS
                                                                 agrees promptly to provide access to all necessary documents
                                                                 and to render reasonable assistance in response to a request
                                                                 by Licensee.

 

		12.	NEGATION OF WARRANTIES AND INDEMNIFICATION

 

		12.01	PHS offers no warranties other than those specified
                                                                 in Article 1.

 

		12.02	PHS does not warrant the validity of the Licensed
                                                                 Patent Rights and makes no representations whatsoever with
                                                                 regard to the scope of the Licensed Patent Rights, or
                                                                 that the Licensed Patent Rights may be exploited without
                                                                 infringing other patents or other intellectual property rights
                                                                 of third parties.

  

		12.03	PHS MAKES NO WARRANTIES,
                                                                 EXPRESSED OR IMPLIED, OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR
                                                                 PURPOSE OF ANY SUBJECT MATTER DEFINED BY THE CLAIMS OF THE LICENSED
                                                                 PATENT RIGHTS OR TANGIBLE MATERIALS RELATED THERETO.

 

		12.04	PHS does not represent that it will commence legal
                                                                 actions against third parties infringing the Licensed Patent
                                                                 Rights.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 11 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		12.05	Licensee shall indemnify and hold PHS, its
                                                                 employees, students, fellows, agents, and consultants harmless
                                                                 from and against all liability, demands, damages, expenses, and
                                                                 losses, including but not limited to death, personal injury,
                                                                 illness, or property damage in connection with or arising out
                                                                 of; a) the use by or on behalf of Licensee, its sublicensees,
                                                                 directors, employees, or third parties of any Licensed Patent
                                                                 Rights; or b) the design, manufacture, distribution, or use
                                                                 of any Licensed Products, Licensed Processes or materials
                                                                 by Licensee, or other products or processes developed
                                                                 in connection with or arising out of the Licensed Patent Rights.
                                                                 Licensee agrees to maintain a liability insurance program
                                                                 consistent with sound business practice.

 

		13.	TERM, TERMINATION; AND MODIFICATION OF RIGHTS

  

	 	13.01	This Agreement is effective when signed by all parties and
    shall extend to the expiration of the last to expire of the Licensed Patent Rights unless sooner terminated as provided
    in this Article 13.

 

	 	13.02	In the event that Licensee is in default in the performance of any material obligations
    under this Agreement, including but not limited to the obligations listed in Article 13.05, and if the default has
    not been remedied within ninety (90) days after the date of notice in writing of such default, PHS may terminate this
    Agreement by written notice and pursue outstanding amounts owed through procedures provided by the Federal Debt Collection
    Act.

 

	 	13.03	
        In the event that Licensee becomes insolvent,
        files a petition in bankruptcy, has such a petition filed against it, determines to file a petition in bankruptcy, or
        receives notice of a third party’s intention to file an involuntary petition in bankruptcy, Licensee shall
        immediately notify PHS in writing. Furthermore, PHS shall have the right to terminate this Agreement
        immediately upon Licensee’s receipt of written notice.

 

	 	13.04	Licensee shall have a unilateral right to terminate this Agreement and/or
    any licenses in any country or territory by giving PHS sixty (60) days written notice to that effect.

 

	 	13.05	PHS shall specifically have the right to terminate or modify, at its option, this
    Agreement, if PHS determines that the Licensee: 1) is not executing the Commercial Development Plan
    submitted with its request for a license and the Licensee cannot otherwise demonstrate to PHS’s satisfaction
    that the Licensee has taken, or can be expected to take within a reasonable time, effective steps to achieve Practical
    Application of the Licensed Products or Licensed Processes; 2) has not achieved the Benchmarks as
    may be modified under Paragraph 9.02; 3) has willfully made a false statement of, or willfully omitted, a material fact in
    the license application or in any report required by the license Agreement; 4) has committed a material breach of a
    covenant or agreement contained in the license; 5) is not keeping Licensed Products or Licensed Processes reasonably
    available to the public after commercial use commences; 6) cannot reasonably satisfy unmet health and safety needs; or 7)
    cannot reasonably justify a failure to comply with the domestic production requirement of Paragraph 5.02 unless waived. In
    making this determination, PHS will take into account the normal course of such commercial development programs conducted
    with sound and reasonable business practices and judgment and the annual reports submitted by Licensee under Paragraph
    9.02. Prior to invoking this right, PHS shall give written notice to Licensee providing Licensee specific
    notice of, and a ninety (90) day opportunity to respond to, PHS’s concerns as to the previous items 1) to 7).
    If Licensee fails to alleviate PHS’s concerns as to the previous items 1) to 7) or fails to initiate corrective
    action to PHS’s satisfaction, PHS may terminate this Agreement.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 12 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		13.06	When the public health and safety so require, and after written
                                                               notice to Licensee providing Licensee a sixty (60)
                                                               day opportunity to respond, PHS shall have the right to
                                                               require Licensee to grant sublicenses to responsible applicants,
                                                               on reasonable terms, in any Licensed Fields of Use under
                                                               the Licensed Patent Rights, unless Licensee
                                                               can reasonably demonstrate that the granting of the sublicense
                                                               would not materially increase the availability to the public of
                                                               the subject matter of the Licensed Patent Rights. PHS
                                                               will not require the granting of a sublicense unless the responsible
                                                               applicant has first negotiated in good faith with Licensee.

 

		13.07	PHS reserves the right according to 35 U.S.C. §209(f)(4)
                                                               to terminate or modify this Agreement if it is determined
                                                               that such action is necessary to meet requirements for public use
                                                               specified by federal regulations issued after the date of the license
                                                               and such requirements are not reasonably satisfied by Licensee.

 

		13.08	Within thirty (30) days of receipt of written notice of PHS’s
                                                               unilateral decision to modify or terminate this Agreement,
                                                               Licensee may, consistent with the provisions of 37 CFR 404.11,
                                                               appeal the decision by written submission to the designated PHS
                                                               official. The decision of the designated PHS official
                                                               shall be the final agency decision. Licensee may thereafter
                                                               exercise any and all administrative or judicial remedies that may
                                                               be available.

 

		13.09	Within ninety (90) days of expiration or termination of this
                                                               Agreement under this Article 13, a final report shall be
                                                               submitted by Licensee. Any royalty payments, including those
                                                               incurred but not yet paid (such as the full minimum annual royalty),
                                                               and those related to patent expense, due to PHS shall become
                                                               immediately due and payable upon termination or expiration. If
                                                               terminated under this Article 13, sublicenses may elect to convert
                                                               their sublicensees to direct licenses with PHS pursuant
                                                               to Paragraph 4.03. Unless otherwise specifically provided for under
                                                               this Agreement, upon termination or expiration of this Agreement,
                                                               Licensee shall return all Licensed Products or other
                                                               materials included Within the Licensed Patent Rights to
                                                               PHS or provide PHS with certification of the destruction
                                                               thereof.

 

		13.10	Non-exclusive License Agreement L-042-00/0 between Licensee
                                                               and PHS shall terminate on the date that this Agreement
                                                               becomes effective.

 

		14.	GENERAL PROVISIONS

 

		14.01	Neither Party
                                                                                   may waive or release any of its rights or interests
                                                                                   in this Agreement except in writing.
                                                                                   The failure of the Government to assert
                                                                                   a right hereunder or to insist upon compliance
                                                                                   with any term or condition of this Agreement
                                                                                   shall not constitute a waiver of that right
                                                                                   by the Government or excuse a similar
                                                                                   subsequent failure to perform any such term
                                                                                   or condition by Licensee.

 

		14.02	This Agreement constitutes the entire agreement between
                                                                 the Parties relating to the subject matter of the Licensed
                                                                 Patent Rights, and all prior negotiations, representations,
                                                                 agreements, and understandings are merged into, extinguished
                                                                 by, and completely expressed by this Agreement.

 

		14.03	The provisions of this Agreement are severable, and
                                                                 in the event that any provision of this Agreement shall
                                                                 be determined to be invalid or unenforceable under any controlling
                                                                 body of law, such determination shall not in any way affect the
                                                                 validity or enforceability of the remaining provisions of this
                                                                 Agreement.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 13 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		14.04	If either Party
                                                                                   desires a modification to this Agreement,
                                                                                   the Parties shall, upon reasonable notice
                                                                                   of the proposed modification by the Party desiring
                                                                                   the change, confer in good faith to determine
                                                                                   the desirability of such modification. No modification
                                                                                   will be effective until a written amendment
                                                                                   is signed by the signatories to this Agreement
                                                                                   or their designees.

 

		14.05	The construction,
                                                                                   validity, performance, and effect of this Agreement
                                                                                   shall be governed by Federal law as applied
                                                                                   by the Federal courts in the District of Columbia.

 

		14.06	All notices required or permitted by this Agreement
                                                                 shall be given by prepaid, first class, registered or certified
                                                                 mail or by an express/overnight delivery service provided by
                                                                 a commercial carrier, properly addressed to the other Party at
                                                                 the address designated on the following Signature Page, or to
                                                                 such other address as may be designated in writing by such other
                                                                 Party. Notices shall be considered timely if such notices are
                                                                 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. Parties
                                                                 should request a legibly dated U.S. Postal Service postmark or
                                                                 obtain a dated receipt from a commercial carrier or the U.S.
                                                                 Postal Service. Private metered postmarks shall not be acceptable
                                                                 as proof of timely mailing,

 

		14.07	This Agreement shall not be assigned by Licensee
                                                                 except: a) with the prior written consent of PHS,
                                                                 such consent not to be withheld unreasonably; or b) as part of
                                                                 a sale or transfer of substantially the entire business of Licensee
                                                                 relating to operations which concern this Agreement. Licensee
                                                                 shall notify PHS within ten (10) days of any assignment
                                                                 of this Agreement by Licensee, and Licensee
                                                                 shall pay PHS, as an additional royalty, one percent
                                                                 (1 %) of the fair market value of any consideration received
                                                                 for any assignment of this Agreement within thirty (30)
                                                                 days of such assignment.

 

		14.08	Licensee agrees in its use of any PHS-supplied
                                                                 materials to comply with all applicable statutes, regulations,
                                                                 and guidelines, including PHS and DHHS regulations
                                                                 and guidelines. Licensee agrees not to use the materials
                                                                 for research involving human subjects or clinical trials in the
                                                                 United States without complying with 21 CFR Part 50 and 45 CFR
                                                                 Part 46. Licensee agrees not to use the materials for
                                                                 research involving human subjects or clinical trials outside
                                                                 of the United States without notifying PHS, in writing,
                                                                 of such research or trials and complying with the applicable
                                                                 regulations of the appropriate national control authorities.
                                                                 Written notification to PHS of research involving human
                                                                 subjects or clinical trials outside of the United States shall
                                                                 be given no later than sixty (60) days prior to commencement
                                                                 of such research or trials.

 

		14.09	Licensee acknowledges that it is subject to and agrees
                                                                 to abide by the United States laws and regulations (including
                                                                 the Export Administration Act of 1979 and Arms Export Control
                                                                 Act) controlling the export of technical data, computer software,
                                                                 laboratory prototypes, biological material, and other commodities.
                                                                 The transfer of such items may require a license from the cognizant
                                                                 Agency of the U.S. Government or written assurances by
                                                                 Licensee that it shall not export such items to certain
                                                                 foreign countries without prior approval of such agency. PHS
                                                                 neither represents that a license is or is not required or
                                                                 that, if required, it shall be issued.

 

		14.10	Licensee agrees to mark the Licensed Products
                                                                 or their packaging sold in the United States with all applicable
                                                                 U.S. patent numbers and similarly to indicate “Patent Pending”
                                                                 status. All Licensed Products manufactured in, shipped
                                                                 to, or sold in other countries shall be marked in such a manner
                                                                 as to preserve PHS patent rights in such countries.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 14 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

		14.11	By entering
                                                                                   into this Agreement,
                                                                                   PHS does not directly or indirectly
                                                                                   endorse any product or service provided, or
                                                                                   to be provided, by Licensee
                                                                                   whether directly or indirectly related
                                                                                   to this Agreement.
                                                                                   Licensee
                                                                                   shall not state or imply that this
                                                                                   Agreement
                                                                                   is an endorsement by the Government,
                                                                                   PHS, any other Government
                                                                                   organizational unit, or any Government
                                                                                   employee. Additionally, Licensee
                                                                                   shall not use the names of NIH,
                                                                                   CDC, PHS,
                                                                                   or DHHS
                                                                                   or the Government or their
                                                                                   employees in any advertising, promotional,
                                                                                   or sales literature without the prior written
                                                                                   consent of PHS.

 

		14.12	The Parties agree to attempt to settle amicably any controversy
                                                                 or claim arising under this Agreement or a breach of this
                                                                 Agreement, except for appeals of modifications or termination
                                                                 decisions provided for in Article 13. Licensee agrees
                                                                 first to appeal any such unsettled claims or controversies to
                                                                 the designated PHS official, or designee, whose decision
                                                                 shall be considered the final agency decision. Thereafter, Licensee
                                                                 may exercise any administrative or judicial remedies that
                                                                 may be available,

 

		14.13	Nothing relating to the grant of a license, nor the grant
itself, shall be construed to confer upon any person any immunity from or defenses under
the antitrust laws or from a charge of patent misuse, and the acquisition and use of rights
pursuant to 37 CFR Part 404 shall not be immunized from the operation of state or Federal
law by reason of the source of the grant.

 

		14.14	Paragraphs 4.03, 8.01, 9.05-9.07, 12.01-12.05, 13.08, 13.09,
                                                                 and 14.12 of this Agreement shall survive termination
                                                                 of this Agreement.

 

SIGNATURES BEGIN ON NEXT PAGE

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 15 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

 

PHS PATENT LICENSE AGREEMENT—EXCLUSIVE

 

SIGNATURE PAGE

 

For PHS:

 

	/s/ Jack Spiegel	 	12/31/2002
	Jack Spiegel, Ph.D.	 	Date
	Director, Division of Technology Development and Transfer	 	 
	Office of Technology Transfer	 	 
	National Institutes of Health	 	 

 

Mailing Address for Notices:

 

Office of Technology Transfer

National Institutes of Health

6011 Executive Boulevard, Suite 325

Rockville, Maryland 20852-3804 U.S.A.

 

For Licensee (Upon, information and belief, the undersigned
expressly certifies or affirms that the contents of any statements of Licensee made or referred to in this document are
truthful and accurate.):

 

	by:	 	 
	 	 	 
	/s/ Ilan Cohn	 	1/29/2003
	Signature of Authorized Official	 	Date
	 	 	 
	ILAN COHN, Ph.D.	 	 
	Printed Name	 	 
	 	 	 
	President & CEO	 	 
	Title	 	 
	 	 	 
	Official and Mailing Address for Notices:	 	 
	 	 	 
	P.O. Box 7537	 	 
	Petach Tikva 49170	 	 
	ISRAEL	 	 

 

Any false or misleading statements made, presented, or
submitted to the Government, including any relevant omissions, under this Agreement and during the course of
negotiation of this Agreement are subject to all applicable civil and criminal statutes including Federal statutes 31
U.S.C. § 3801-3812 (civil liability) and 18 U.S.C. §  1001 (criminal liability including fine(s) and/or
imprisonment).

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249.01/0 with CanFite

Model 980611a Page 16 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDIX A—Patent(s) or Patent
Application(s)

 

Patent(s) or Patent Application(s):

 

U.S.P.A. 08/091.109 filed July 13, 1993

U.S.P.A. 08/163,324 filed December 6, 1993 which a continuation-in-part
of 08/091,109

U.S.P.A. 08/274,628 filed July 13, 1994 which is a continuation-in-part
of 08/163,324 and which issued June 30, 1998 as U.S. Patent 5,773,423

PCT/US94/07835, based on 08/274,628 and filed July 13, 1994

European patent application 94923445.4 with priority to PCT/US94/07835

National patents in Europe based on said European application.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 17 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDlX B—Licensed Fields of Use
and Territory

 

Licensed Fields of Use:

 

		I.	Any A3 agonist falling within the Licensed Patent Rights for the therapeutic treatment of the following indications:

 

		a.	Clinical indication that are of prime interest to Licensee (“the Prime Indications”) and for which
there are specific benchmarks for performance under Appendix F:

 

		1.	Myeloprotection - an adjunctive treatment to chemotherapy for the purpose of reducing myelotoxicity;

		2.	Anti-cancer - a treatment intended to inhibit growth of cancer cells;

		3.	Stem cell mobilization - to induce migration of progenitor cells to the peripheral blood system for their harvesting
and subsequent engraftment in a recipient (typically an autologous engraftment);

 

		b.	Other clinical indications (“the non-prime indications”)
                                                              for which specific benchmarks for performance will be submitted
                                                              as required by licensee:

 

		1.	Treatment of viral infections –a treatment
                                                              intended to alleviate viral infections or the symptoms associated
                                                              therewith;

		2.	Arthritis – a treatment intended to alleviate
                                                              the disease or the symptoms associated therewith.

 

		II.	The following A3 agonist compounds falling within the Licensed Patent Rights: N6
                                                           -(3-iodobenzyl)-adenosine- 5’-N-methyluronamide (IB-MECA) and
                                                           2-Cl-N6-(3-iodobenzyl)-adenosine-5’-N-methyluronamide (C1-IB-MECA) for all therapeutic
                                                           uses.

 

Licensed Territory: Worldwide

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 18 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDIX C—Royalties

 

Pursuant to Section 6.01, Licensee agrees to pay to
PHS a noncreditable, nonrefundable license issue royalty in the amount of Two Hundred Twenty-Five Thousand Dollars ($225,000).
The license issue royalty shall be payable according to the following schedule:

 

A first payment of Fifty Thousand Dollars ($50,000)
shall become due and payable within 30 days of execution of this license.

 

A second payment of Seventy Five Thousand Dollars
($75,000) shall become due and payable on the six month anniversary date of execution this license.

 

A third and final payment of One Hundred Thousand
Dollars ($100,000) shall become due and payable on the one-year anniversary date of the execution of this license.

 

Pursuant to Section 6.02, Licensee agrees to pay to
PHS a nonrefundable minimum annual royalty in the amount of fifty thousand dollars ($50,000).

 

Pursuant to Section 6.03, Licensee agrees to pay PHS
earned royalties on Net Sales by or on behalf of Licensee and its sublicensees, calculated on an annual basis in each
calendar year and graded as follows:

 

Royalties of five and one half percent (5.5%) on
an amount of annual Net Sales of Licensed Products or on practice of Licensed Processes in the Licensed Territory
of up to and including twenty-five million U.S. dollars ($25,000,000);

 

Royalties of four and one half percent (4.5%) on
an amount of annual Net Sales of Licensed Products or on practice of Licensed Processes in the Licensed Territory
between twenty five million U.S. dollars ($25,000,000) and one hundred million US Dollars ($ 100,000,000);

 

Royalties of four percent (4.0%) on an amount of
annual Net Sales of Licensed Products or on practice of Licensed Processes in the Licensed Territory of greater
than and including one hundred million U.S. dollars ($100,000,000).

 

Licensee shall be entitled to a reduction
in the earned royalty rate to be paid to PHS in an amount equal to the earned royally rate Licensee must pay to
Aderis Pharmaceuticals Inc. under the agreement which became effective May 6, 2002 for the manufacture and sale of Licensed
Products or practice of Licensed Processes in the Licensed Territory.

 

Pursuant to Section 6.04, Licensee agrees to pay PHS
benchmark royalties as follows:

 

Twenty Five Thousand ($25,000) Dollars payable within
sixty (60) days after the initiation of the first Phase I clinical trials (or its equivalent) per indication.

 

Seventy Five Thousand ($75,000) Dollars payable within
sixty (60) days after the initiation of the first Phase II clinical trials (or its equivalent) per indication.

 

One Hundred Thousand ($100,000) Dollars payable within
sixty (60) days after the initiation of the first Phase III clinical trials (or its equivalent) per indication.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 19 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

Five Hundred Thousand ($500,000) Dollars payable within
ninety (90) days after each FDA (or its equivalent) approval in each major market area (U.S.A., Europe, or Japan) per indication.

 

Pursuant to Section 6.05, Licensee agrees to pay PHS
sublicensing royalties as follows;

 

Twenty percent (20%) of any monetary consideration
received from each sublicense, but not including royalties on Net Sales for which royalties will only be due under Section
6.03. Licensee may credit benchmark royalties due under Section 6.04 against sublicensing royalties due on consideration
received by Licensee from sublicensee for milestones achieved by a sublicensee when such milestones are substantially similar
to the benchmarks described above for Section 6.04.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 20 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDIX D—Modifications

 

PHS and Licensee agree to the following modifications
to the Articles and Paragraphs of this Agreement:

 

None

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 21 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDIX F—Commercial Development
Plan

 

See “Business Plan” dated November 11, 2001 included
with Application. Benchmarks for performance specifically listed in Appendix E are controlling if in conflict with this or any
other “Business Plan”.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 23 of 23, December 3, 2002, FILE: L249010FINAL

 

    	 

    	 

    

 

APPENDIX E—Benchmarks and Performance

 

Licensee agrees to the following Benchmarks for
its performance under this Agreement and, within thirty (30) days of achieving a Benchmark, shall notify PHS
that the Benchmark has been achieved.

 

Regulatory Benchmarks for the Prime Indications

 

		I.	For the Stem cell mobilization therapeutic indication (pre-clinical and Phase I studies using IB-MECA have already been
accomplished)

 

		1.	Initiate FDA Phase II/III clinical trials or foreign equivalent clinical trials by the end of the fourth quarter of 2003.

		2.	Submission of a New Drug Application (NDA) (or its equivalent) to the FDA (or its foreign equivalent) for a Licensed Product
or Process by the end of the fourth quarter of 2004.

 

		II.	For the Myeloprotection therapeutic indication (pre-clinical and Phase I studies using IB-MECA have already been accomplished):

 

		1.	Initiate FDA Phase II clinical trials or foreign equivalent clinical trials by the end of the fourth quarter of 2003.

		2.	Initiate FDA Phase III clinical trials or foreign equivalent clinical trials by the end of the fourth quarter of 2004.

		3.	Submission of a New Drug Application (NDA) (or its equivalent) to the FDA (or its foreign equivalent) for a Licensed Product
or Process by the end of the second quarter of 2006.

 

		III.	For the Anti-cancer therapeutic indication (pre-clinical and Phase I studies using IB-MECA have already been accomplished):

 

		1.	Initiate FDA Phase II clinical trials or foreign equivalent clinical trials by the end of the first quarter of 2003.

		2.	Initiate FDA Phase III clinical trials or foreign equivalent clinical trials by the end of the third quarter of 2004.

		3.	Submission of a New Drug Application (NDA) (or its equivalent) to the FDA (or its foreign equivalent) for a Licensed Product
or Process by the end of the first quarter of 2006.

 

CONFIDENTIAL PHS Patent License Agreement—Exclusive
L-249-01/0 with CanFite

Model 980611a Page 22 of 23, December 3, 2002, FILE: L249010FINALExhibit 4.9

 

PUBLIC
HEALTH SERVICE

 

FIRST AMENDMENT TO EXCLUSIVE PATENT LICENSE
AGREEMENT - L-249-2001/0

 

AMENDMENT L-249-2001/1

 

This Amendment, L-249-2001/1, (“First
Amendment”) of the Exclusive Patent License L-249-2001/0 (“Agreement”) is made between the National Institutes
of Health (“NTH”), the Centers for Disease Control and Prevention (“CDC”), or the Food and Drug Administration
(“FDA”), hereinafter singly or collectively referred to as (“PHS”), agencies of the United States Public Health
Service within the Department of Health and Human Services (“DHHS”) through the Office of Technology Transfer,
NIH, having an address at 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804, U.S.A. and Can-Fite BioPharma,
Ltd. having offices at the address indicated on the Signature Page, hereinafter referred to as “Licensee”.

 

Whereas, Licensee desires to add
an option to discontinue or drop development of a Licensed Field of Use without penalty upon written notification of PHS
of a decision to do so;

 

Whereas, Licensee desires to amend the existing Benchmarks
included in Appendix E - Benchmarks and Performance of the Agreement.

 

Whereas, Licensee desires to add Benchmarks for “Non-prime”
Indications to Appendix E of the Agreement.

 

Whereas, PHS and Licensee are mutually willing
to amend the Agreement to accommodate the desire for providing an option to discontinue or drop a Licensed Field of Use
without penalty and for modifying Appendix E - Benchmarks and Performance.

 

Now therefore, PHS and Licensee, intending to be bound,
hereby mutually agree to the following:

 

		A.	The Agreement shall be modified as follows:

 

1.     Paragraph 9.02
shall have added the following two sentences:

 

Licensee may discontinue or drop commercial
development of any Licensed Field of Use identified in Appendix B provided that Licensee notifies PHS
in writing within thirty (30) days of making such a decision, and provided that one or more of the remaining Licensed Fields
of Use continues to be developed. Upon such notification, PHS will amend the Agreement to reflect this removal
from the Licensed Fields of Use and Benchmarks.

 

2.    Appendix E - Benchmarks
and Performance shall be deleted in its entirety and be replaced with a new Appendix E - Benchmarks and Performance that
shall now read:

 

APPENDIX E -Benchmarks and Performance

 

Licensee agrees to the following Benchmarks for
its performance under this Agreement and, within thirty (30) days of achieving a Benchmark, shall notify PHS
that the Benchmark has been achieved.

 

Regulatory Benchmarks for the Prime Indications

 

		I.	For the Myeloprotection therapeutic indication:

 

		1.	Initiate FDA Phase I or Phase I/II clinical trial or foreign equivalent by the end of third quarter 2006.

 

		2.	Initiate FDA Phase lib clinical efficacy trial or foreign equivalent by the end of fourth quarter 2007.

 

		3.	Initiate FDA Phase III clinical trial or foreign equivalent by the end of second quarter 2009.

 

A-173-2004

First Amendment (L-249-2001/1) of Exclusive Patent License Agreement
(L-249-2001/0)

PHS: Can-Fite Biopharma, Ltd. -FINAL [08/02/05]

Page l of 3

 

    	 

    	 

    

 

 FIRST
AMENDMENT TO PHS LICENSE AGREEMENT L-249-2001/0

 

		4.	Submit a New Drug Application (NDA) (or its equivalent) to the FDA (or its foreign equivalent) for a Licensed Product or Process
by the end of fourth quarter 2010.

 

		II.	For the Stem Cell Immobilization therapeutic indication:

 

		1.	Initiate FDA Phase I clinical trial or foreign equivalent by the end
of second quarter 2007.

		2.	Initiate FDA Phase II clinical efficacy trial or foreign equivalent
by the end of first quarter 2008.

		3.	Initiate FDA Phase II clinical trial or foreign equivalent by the end
of second quarter 2009.

		4.	Submit a New Drug Application (NDA) (or its equivalent) to the FDA (or its foreign equivalent) for a Licensed Product or Process
by the end of fourth quarter 2010.

 

		III.	For the Anti-cancer therapeutic indication (for
Cl-IB-MECA):

 

		1.	Initiate FDA Phase I or Phase I7II clinical trial or foreign equivalent by the end of third quarter 2006.

		2.	Initiate FDA Phase lib clinical efficacy trial or foreign equivalent by the end of second quarter 2007.

		3.	Initiate FDA Phase III clinical trial or foreign equivalent by the end
of second quarter 2008.

		4.	Submit a New Drug Application (NDA) (or its equivalent)
to the FDA (or its foreign equivalent) for a Licensed Product or Process by the end of second quarter 2010.

 

Regulatory Benchmarks for the Non-Prime
Indications

 

		I.	For the Anti-viral therapeutic indication:

 

		1.	Initiate FDA Phase I clinical trials or foreign equivalent by the end
of second quarter 2007.

		2.	Initiate FDA Phase II clinical trials or foreign equivalent by the end
of fourth quarter 2008.

		3.	Initiate FDA Phase III clinical trials or foreign equivalent by the
end of second quarter 2010.

		4.	Submit a New Drug Application (NDA) by the end of fourth quarter 2012.

 

		II.	For the Arthritis therapeutic indication: (Phase I and II studies
using IB-MECA have already been accomplished for this indication):

 

		1.	Initiate FDA Phase lib clinical efficacy trials or foreign equivalent
in rheumatoid arthritis by the end of second quarter of 2006.

		2.	Initiate FDA Phase III clinical trials or foreign equivalent by the
end of fourth quarter of 2007.

		3.	Submit a New Drug Application (NDA) (or its equivalent) to the FDA (or
its foreign equivalent) for a Licensed Product or Process by the end of fourth quarter 2009.

 

		B.	Licensee agrees to pay PHS a nonrefundable First Amendment
execution fee in the amount of twenty five thousand ($25,000) dollars. This First Amendment Execution Fee will be payable within
thirty (30) days of conclusion of an equity or debt financing from non-affiliated third parties or a merger with or an acquisition
by another corporation.

 

		C.	All terms and conditions of the Agreement not herein amended
remain binding and in effect;

 

		D.	The execution date of this First Amendment shall be the date
when it has been signed by all parties; and

 

		B.	The Agreement, and this First Amendment constitute the
entire understanding between PHS and Licensee and supersede all prior agreements and understandings with respect
to Materials and Licensed Products.

 

A-173-2004

First Amendment (L-249-2001/1) of Exclusive Patent License Agreement
(L-249-2001/0)

PHS: Can-Fite Biopharma, Ltd. -FINAL [08/02/05]

Page 2 of 3

 

    	 

    	 

    

 

SIGNATURES
BEGIN ON THE NEXT PAGE

FIRST AMENDMENT TO PHS LICENSE AGREEMENT
L-249-2001/0

 

SIGNATURE PAGE

 

For PHS:

 

	/s/ Steven M. Ferguson	 	8/4/05
	Steven M. Ferguson	 	Date
	Director, Division of Technology Development and Transfer	 	 
	Office of Technology Transfer	 	 
	National Institute of Health	 	 

 

Mailing Address for Notices:

 

Chief, License Monitoring & Enforcement Branch

Office of Technology Transfer

National Institutes of Health

6011 Executive Boulevard, Suite 325

Rockville, Maryland 20852-3804 U.S.A.

 

For Licensee (Upon, information and belief, the undersigned
expressly certify or affirm that the contents of any statements of Licensee made or referred to in this document are truthful
and accurate.):

 

	By:	 	 
	 	 	 
	/s/ Pnina Fishman	 	August 15, 2005
	Pnina Fishman	 	Date
	Chief Executive Officer	 	 

 

Official and Mailing Address for Notices:

 

Can-Fite BioPharma, Ltd.

10 Bareket Street

Kiryat Matalon, P.O. Box 7537

PetachTikva 49170

ISRAEL

 

A-l 73-2004

First Amendment (L-249-2001/1) of Exclusive Patent License Agreement
(L-249-2001/0)

PHS: Can-Fite Biopharma, Ltd. -FINAL [08/02/05]

Page 3 of 3

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00221-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00221-of-00352.parquet"}]]