Exhibit
10.5


 


Certain
confidential information contained in this document, marked by brackets and asterisk, has been omitted pursuant to Item 601(b)(10)(iv)
of Regulation S-K, because it (i) is not material and (ii) would be competitively harmful if publicly disclosed


 


Agreement


 


This
Agreement (the “Agreement”) is made and entered into this 7th day of June 2022 (“Effective Date”)
by and between Polyrizon Ltd., Company Number 513637025 located at 5 Hatidhar St. R’annana, Israel. (“Polyrizon”),
and NurExone Biologic Ltd., Company No. 516209202 located at 9 Mezada St., Bney Brak, Israel (“Nurexone”). (collectively
referred to as “Parties” and each may be referred individually as a “Party”).


 


	WHEREAS	Polyrizon
                                            operates and holds the know-how, inter-alia, in the field of creating formulations for therapeutic
                                            delivery Products.; and



		 	 



	WHEREAS	Nurexone
                                            operates and holds the know-how, inter-alia, in the field of CNS indications including Spinal
                                            Cord Injury (SCI) treatment, based on a revolutionary siRNA loaded into extracellular vesicles
                                            (EV) administration which serves as drug platform technology to treat damage in the Central
                                            Nerve System (CNS) including Spinal Cord Injuries (SCI) with siRNA-PTEN Loaded exosome (exoPTEN);
                                            and



		 	 



	WHEREAS	The
                                            Parties wish to enter into this Agreement and to define the terms and conditions for the
                                            co-development of a formulation for intranasal application based exosomes for spinal injuries
                                            as a model for treating CNS indications with loaded exosomes (the “Product”)
                                            and the manufacturing, use, commercialization and sales efforts of the Product, all in accordance
                                            with and subject to the provisions of this Agreement;



 


NOW,
THEREFORE, in consideration of the mutual promises and covenants set forth herein, the parties hereby agree as follows:


 


	1.	Definitions
                                            and interpretation



 


In
this Agreement:


 


		1.1.	Unless
                                            otherwise specified, words importing the singular include the plural, words importing any
                                            gender include every gender, and words importing persons include bodies corporate and unincorporated;
                                            and in each case vice versa.



 


		1.2.	Reference
                                            to Clauses and other provisions are references to Clauses and other provisions of this Agreement.



 


		1.3.	The
                                            headings shall not affect the interpretation of this Agreement.



 


		1.4.	The
                                            expressions “hereunder”, “hereto”, “herein”, “hereof”
                                            and similar expressions relate to this entire Agreement and not to any particular provision
                                            thereof.



 






    1


    


    

 


	2.	Co-Development
                                            and Joint Business Efforts



 


		2.1.	The
                                            purpose of this Agreement is to set out the terms and conditions under which the Parties
                                            will fully co-develop the Product. As such, the Parties shall use their best efforts to carry
                                            out their respective obligations with respect to the co-development activities as set forth
                                            in this Agreement and in accordance with the agreed Specifications (as defined below). The
                                            Parties shall at all times during the Term of this Agreement cooperate and collaborate in
                                            good faith with respect to the co- development activities and implementation of the Development
                                            Plan (as defined below) and thereafter with respect to the marketing and sales efforts of
                                            Nurexone.



 


		2.2.	As
                                            of the execution of this Agreement the Parties have appointed the following representatives
                                            to the joint project team (the “Steering Committee”):



 


		2.2.1.	Polyrizon’s
                                            representative shall be Polyrizon’s CEO and/or CRO.



 


		2.2.2.	Nurexone’s
                                            representative shall be Nurexone’s CEO and/or R&D Director.



 


		2.3.	The
                                            Steering Committee shall manage the joint development activities and will jointly supervise
                                            over the business and development processes of the project in order to meet the detailed
                                            development plan set out in Annex A to this Agreement (the “Development
                                            Plan”).



 


		2.4.	In
                                            addition to the above, the Steering Committee shall set out and establish the specifications
                                            of the Product and of each Work Order (the “Specifications”).



 


		2.5.	It
                                            is hereby agreed that the Development Plan will be executed by both Parties will signing
                                            detailed work orders which will specify the required tasks and timelines (the “Work
                                            Order”).



 


		2.6.	It
                                            is hereby agreed that, in the event a Party is required to provide certain information, material
                                            or other input to the other Party in order to complete a Work Order and fails to do so, the
                                            deadline for such Work Order will be postponed in correspondence with the delay caused by
                                            such failing party.



 


		2.7.	Each
                                            Party agrees and undertakes to provide its representatives to the Steering Committee with
                                            full authority to make any decision required in order to facilitate the advancement of the
                                            collaboration.



 


		2.8.	It
                                            is hereby agreed that all decisions with regards to the Product will be made unanimously
                                            by decision of the parties’ representatives to the Steering Committee, provided however,
                                            that the decisions will be subject to each Party’s internal corporate governance requirements
                                            and board approvals if applicable.



 






    2


    


    

 


	3.	Information
                                            and Reports



 


		3.1.	The
                                            Parties will prepare quarterly reports to be provided to the Steering Committee which shall
                                            include all development activities and any other relevant activities carried out by each
                                            party in furtherance of the joint project, and all relevant information required by the Steering
                                            Committee and reasonably necessary in order to ascertain and analyse the status of the joint
                                            project.



 


		3.2.	In
                                            addition, each Party shall be entitled to receive any information required by such Party,
                                            in connection with this Agreement and the Product, from the Steering Committee.



 


	4.	Costs
                                            and Expenses



 


		4.1.	The
                                            Parties hereby agree that Nurexone shall bear all costs and expenses incurred in the development
                                            and establishment of the joint business activities and in the co- development of the Product.



 


		4.2.	Nurexone
                                            shall pay Polyrizon the agreed upon amount set out in each signed Work Order.



 


		4.3.	Development
                                            Milestone Fee. Nurexone shall pay to Polyrizon a total of three million three hundred
                                            and fifty thousand dollars ($3,350,000.00) (the “Development Milestone Fee”)
                                            in consideration for and conditioned upon the completion of each milestone as set forth below(“Milestone”).
                                            Polyrizon will issue to Nurexone an invoice for the portion of the Development Milestone
                                            Fee then due and Nurexone shall pay the Development Milestone Fee in accordance with the
                                            following:



 


		4.3.1.	First
                                            Milestone – Preclinical safety studies. Nurexone shall preform preclinical safety
                                            tests on the Product. Upon a successful preclinical safety test Nurexone shall pay Polyrizon
                                            an amount of US$ 100,000.



 


		4.3.2.	Second
                                            Milestone – Phase IIa Clinical Trial. Nurexone shall preform phase Iia clinical
                                            trials on the Product. Upon completion of phase Iia clinical trial Nurexone shall pay Polyrizon
                                            an amount of US$ 400,000.



 


		4.3.3.	Third
                                            Milestone – Phase III Clinical Trial. Nurexone shall preform phase III clinical
                                            trials on the Product. Upon completion of phase III clinical trial Nurexone shall pay Polyrizon
                                            an amount of US$ 600,000.



 


		4.3.4.	Fourth
                                            Milestone – Regulatory Approval in U.S. the Parties shall submit the Product for
                                            FDA approval in the United States. Upon receipt of the approval of the FDA Nurexone shall
                                            pay Polyrizon an amount of US$ 1,125,000.



 






    3


    


    

 


		4.3.5.	Fifth
                                            Milestone – Regulatory Approval in the EU. The Parties shall submit the Product
                                            for approval of an EU regulatory body. Upon receipt of the approval of the relevant EU regulatory
                                            body Nurexone shall pay Polyrizon an amount of US$ 1,125,000.



 


It
is agreed that Nurexone shall notify Polyrizon within one business days as of the completion of each Milestone that is carried out by
Nurexone. In addition, it is hereby agreed that the Steering Committee shall provide updates to Polyrizon as to the progress of each
Milestone that is being carried out by Nurexone.


 


Upon
the completion of each Milestone: (i) Nurexone shall pay to Polyrizon the applicable Development Milestone Fee as set out in Section
4.3.1-4.3.5 within 14 business days as of Nuerxone’s notice of completing each applicable Milestone, unless the fee for such Milestone
is to be converted according to the provisions of Section 4.6.2 below. And (ii) Polyrizon shall transfer to Nurexone the Work Product
(as defined below) developed created or made during the applicable Milestone.


 


		4.4.	License
                                            Fee-Royalties. In addition to the Development Milestone Fee, and in consideration of
                                            the license rights granted to Nurexone as set forth under section 6 herein, Nurexone shall
                                            pay to Polyrizon the following royalties (the “Royalties”):



 


		4.4.1.	For
                                            sales of the Product by Nurexone that generate an income of between US$ 50,000 and US$ 2,500,000
                                            Nurexone shall pay Polyrizon an amount equal to 2.25% of the Net Income actually received
                                            by Nurexone.



 


		4.4.2.	For
                                            sales of the Product by Nurexone that generate an income of between US$ 2,500,000 and US$
                                            10,000,000 Nurexone shall pay Polyrizon an amount equal to 2.75% of the Net Income actually
                                            received by Nurexone.



 


		4.4.3.	For
                                            sales of the Product by Nurexone that generate an income greater than US$ 10,000,000 Nurexone
                                            shall pay Polyrizon an amount equal to 3.25% of the Net Income actually received by Nurexone.



 


		4.4.4.	For
                                            sales of the Product by a sublicensee of Nurexone, Nurexone shall pay Polyrizon an amount
                                            equal to 35% of the income actually received by Nurexone from the sublicensee.



 


For
the purpose of this Agreement the Term “Net Income” means the profit earned by Nurexone from the sale of the product
less the expenses paid in the process of selling the Product. For the purpose of determining the Net Income under this Agreement it is
agreed that only the following expenses shall be taken into account: direct production expenses of the Product, direct marketing expenses
of the Product, direct distribution expenses of the product.


 


For
avoidance of doubt it is hereby agreed that salaries of employees of Nurexone and on-going payments to sales advisors shall not be considered
expenses to be deducted.


 






    4


    


    

 


		4.5.	Nurexone
                                            shall pay such Royalties to Polyrizon within 14 business days as of the end of each calendar
                                            quarter. Nurexone shall keep and maintain, and Polyrizon shall have the right to access and
                                            audit, such books and records as reasonably necessary to confirm Nurexone’s Net Income
                                            and performance of its payment obligations under this Section 4.



 


		4.6.	Payment
                                            Method.



 


		4.6.1.	All
                                            amounts payable under this Agreement shall be made by bank-wire transfer in immediately available
                                            funds to an account that Polyrizon designates, or such other reasonable method as the parties
                                            may mutually agree upon from time to time. Any payments or portions of payments due under
                                            this Agreement that are not paid by the date such payments are due under this Agreement shall
                                            bear interest equal to the greater of (a) twelve percent (12%) per annum, or (b) the maximum
                                            rate permitted by law, pro rated to reflect the number of days such payment is delayed.



 


		4.6.2.	Notwithstanding
                                            the foregoing in Section 4.6.1, The Parties Agree that the Development Milestone Fee set
                                            out in Section 4.3.1 and 4.3.2 above may be converted into shares of Nurexone, at the sole
                                            discretion of Polyrizon. The Development Milestone Fee eligible for conversion will not exceed
                                            the aggregate amount of US$ 350,000. The conversion price will be (i) in the event the Nurexone
                                            Shares are publicly traded, the quoted price per share on the day of conversion or (ii) in
                                            the event Nurexone shares are not publicly traded, the price per share in the most recent
                                            investing round completed before the date of conversion.



 


	5.	Joint
                                            Intellectual Property



 


In
this Agreement the following capitalized terms have the meanings set forth below:


 


“Intellectual
Property” means all intellectual, moral, industrial and/or proprietary property and rights now or hereafter recognized
under any applicable law or in equity anywhere in the world, whether issued or pending, registered or unregistered, patentable or
unpatentable, including, but not limited to (i) all forms of patents and utility models; (ii) inventions, discoveries,, trade
secrets and other proprietary rights, including ideas, formulas, compositions (whether patentable or unpatentable and whether or not
reduced to practice), know-how, manufacturing and production processes and techniques, research and development information,
drawings, specifications, designs, plans, technical data, rights in algorithms, binary codes, business methods, concepts, customers,
distributers and suppliers lists, ideas; (vi) computer software (source and object code), modules, libraries, code, or other
components, and documentation for the foregoing; (iii) rights associated with works of authorship, including but not limited to
copyrights and mask works; (iv) trademarks and service marks, trade names, domain name registration; (v) designs (whether or not
capable of registration), design rights; (vi) database rights; (vii) trade secrets and know how; (viii) all rights to confidential
or proprietary information; (ix) use cases and business models; and
with respect to the intellectual property included in paragraphs (i) to and including (ix)
above - any rights analogous to those mentioned herein; all derivative works thereof, any other intellectual property rights, moral rights
or industrial property rights not otherwise set forth in (i) through (ix) above; and any current or future applications, renewals, extensions,
provisionals, continuations, continuations-in-part, divisions, re- exams and reissues thereof; the right to apply to any of the above;
and all of the tangible embodiments thereof.


 






    5


    


    

 


“Intellectual
Property Rights” means all rights, title and interest in and to any Intellectual Property.


 


“Pre-Existing
IP” means any know-how, concepts, tools, processes, methodologies, Intellectual Property and other information or materials
existing on the Effective Date held and owned by a Party hereto, and any modifications, derivatives, enhancements or changes thereto.


 


		5.1.	All
                                            Intellectual Property jointly made, developed, conceived, first reduced to practice, fixed
                                            in any tangible medium of expression or created by the Parties during the term of this Agreement
                                            and in connection with the Product (“Joint Intellectual Property”), will
                                            be the joint property of and the entire right, title and interest is hereby assigned jointly
                                            to both Parties, and neither Party may enjoy all rights and privileges or ownership of such
                                            joint property without accounting to the other.



 


		5.2.	Each
                                            Party shall solely own and shall retain all Intellectual Property Rights in its Pre-Existing
                                            IP.



 


		5.3.	“Work
                                            Product” means all results of the joint project carried out by the Parties under
                                            this Agreement and shall include, but not be limited to, software including software source
                                            code and object code, and derivative works, inventions, discoveries, improvements, designs,
                                            concepts, techniques, methods, products, content, processes, derivative works, domain names,
                                            formulae, specifications, know how, computer software programs, databases, mask works, logos
                                            and trade secrets, whether or not patentable, copyrightable or protectable as trade secrets,
                                            as well as business plans, file layouts, and manufacturing information. The Steering Committee
                                            shall prepare and maintain adequate and current records of all Work Product, created in the
                                            course of performance hereunder, and all technical manuals and documentation, created conceived,
                                            reduced to practice, authored, developed or delivered by the Parties or their employees,
                                            agents, consultants, contractors and representatives including without limitation any third
                                            party service providers approved by both Parties, either solely or jointly with others, during
                                            and in connection with the performance of this Agreement and co-development of the Product,
                                            which records shall be and remain the joint property of both Parties.



 






    6


    


    

 


		5.4.	The
                                            Parties shall jointly agree on appropriate ways to protect the Joint Intellectual Property
                                            over the Work Product of the joint project, including by applying for and enforcing patents,
                                            copyrights, mask work rights, and other legal protections for the Work Product in any and
                                            all countries. The Parties shall jointly appoint a team that will carry out all activities
                                            necessary for the legal protection of their joint rights to the Product and to any Work Product,
                                            on behalf of the Parties and execute and file any document needed to for securing any patent,
                                            copyright, trademark, trade secret, any applications regarding same or any other right or
                                            protection relating to any proprietary information (including Work Product), and to do all
                                            other lawfully permitted acts to further the prosecution and issuance of patents, copyrights,
                                            trademarks, trade secrets or any other right or protection relating to any proprietary information
                                            (including Work Product).



 


		5.5.	For
                                            avoidance of doubt, it is hereby clarified that both Parties will only be entitled to enjoy
                                            the Joint Intellectual Property in the Product and/or the Work Products jointly in a 50/50
                                            basis and no Party shall enjoy such rights and/or derive any income or profit from such rights
                                            without ensuring that the other Party receives its share of such profit or income as shall
                                            be agreed between the Parties in advance.



 


		5.6.	Except
                                            as provided in this Section 5, and subject to the license expressly granted under this Agreement,
                                            each Party shall continue to own all Pre-Existing IP owned by it prior to the Effective Date
                                            and shall own all Intelctual Property Rights developed by that Party following the Effective
                                            Date, provided such Intellectual Property Rights were created or acquired not in connection
                                            to this Agreement and\or the Product.



 


		5.7.	The
                                            Parties hereby agree that no applications, capabilities, solutions or other Intellectual
                                            Property in direct connection with each party’s Pre-Existing IP shall be developed
                                            by the other party (or on its behalf), other than in connection with the Product, without
                                            the prior written consent of the other Party. It is further agreed that any such development
                                            shall not be made unless the Parties agree in advance and in writing on ownership of any
                                            such development, as evidenced by an agreement signed by both Parties.



 


	6.	IP
                                            and Product Licenses



 


		6.1.	General.
                                            Except as set forth in this Section 6, neither Party grants to the other Party any rights
                                            or licenses under its Intellectual Property Rights.



 


		6.2.	Limited
                                            License Granted by Polyrizon.



 


		6.2.1.	Grant.



 


		6.2.2.	Grant
                                            of License. Subject to the terms of this Agreement, Polyrizon grants to Nurexone



 


		(i)	an
                                            exclusive worldwide, nontransferable, perpetual, irrevocable, royalty bearing (under Section
                                            4 above), right and license, under Polyrizon’s rights in the Joint Intellectual Property,
                                            for, and in conjunction with the Product, and as required to develop, use, make, manufacture
commercialize, and to otherwise dispose of the Product without restriction as Nurexone may deem fit; and






 


		(ii)	a
                                            non-exclusive, worldwide, nontransferable, perpetual, irrevocable, royalty bearing (under
                                            Section 4 above), right and license, under Polyrizon’s Pre-Exiting IP incorporated
                                            in, or on the basis of, or otherwise required for Nurexone to fully effect its license under
                                            subsection (i) above, in conjunction with the Product, the Joint Intellectual Property and
                                            the Work Product/s.



 






    7


    


    

 


		6.2.3.	The
                                            licenses above shall include without limitation the following licenses:



 


		(i)	To
                                            make, have made, use, offer for sale, sell, import and export the Product; and



 


		(ii)	To
                                            use, copy, modify, create derivative works of the Product, and any other Work Product as
                                            needed to fully effect the right granted above.



 


		6.2.4.	Sublicenses.
                                            Nurexone may sublicense the rights in the Product, which shall not thereafter be sublicensable
                                            (for the purpose of clarification, a sublicensee of Nurexone will not be able to sublicense
                                            the license under this Agreement other than with Polyrizon’s consent). In the event
                                            of sublicensing by Nurexone in accordance with this Section 6, Nurexone shall be fully responsible
                                            and liable for the protection of the rights under the sub-license and shall ensure that any
                                            such sub-licensee executes a license agreement which includes terms and conditions at least
                                            as restrictive as this Agreement for the purpose of protecting the rights being licensed
                                            under this Agreement and the Intellectual Property Rights of the Parties.



 


If
a Party grants a sublicense of the license under this Section 6, such Party shall cause its sublicensee to comply with all obligations
of such Party hereunder; provided that such Party shall at all times be fully responsible for the performance of such sublicensee.


 


	7.	Non
                                            – Compete and Non-Circumvention



 


		7.1.	Unless
                                            it has obtained the prior written consent of the other party, each party hereby undertakes,
                                            either alone or jointly, with, through or on behalf of any person, and/or entity directly
                                            or indirectly, not to solicit or contact with a view of engagement or employment by any person,
                                            any employee, officer or manager of the other Party or any person and/or entity who has been
                                            an employee, officer, manager, consultant, of the other Party within the previous two-year
                                            period.



 


		7.2.	Each
                                            of these restrictions is an entirely separate and independent restriction on each Party and
                                            the validity of one restriction shall not be affected by the validity or unenforceability
                                            of another.



 






    8


    


    

 


		7.3.	Each
                                            party considers the restrictions in this Section 7 to be reasonable and necessary for the
                                            protection of the interests of the joint project. If any such restriction shall be held to
                                            be void but would be valid if deleted in part or reduced in application, such restriction
                                            shall apply with such deletion or modification as may be necessary to make it valid and enforceable.



 


		7.4.	The
                                            covenants set out in this Section 7 shall continue to apply to the Parties during the term
                                            of this Agreement and for a period of 24 months from the date of its termination for any
                                            reason whatsoever. The covenants shall be construed during this period by reference to the
                                            joint business carried out by the Parties, customers, employees, officers or managers or
                                            contracting parties of the Parties as at or during the twelve months period prior to the
                                            date of termination.



 


	8.	Confidentiality



 


		8.1.	Each
                                            of the Parties undertakes to the other that they will not at any time hereafter use or divulge
                                            or communicate to any person other than those of their senior executives and those members
                                            of their professional advisors who, in each case, need to know any confidential information
                                            they may come to know as a result of the performance of this Agreement – such information
                                            is defined as confidential (“Confidential Information”) and includes,
                                            but is not restricted to, names, contact information, process blueprints, methodologies,
                                            proprietary knowledge, know how, information related to the respective business activities
                                            of the parties, and/or the joint project, pricing information, sales and marketing information,
                                            financial information, business plans, budgets, etc. - and they shall use all reasonable
                                            endeavours to prevent the publication or disclosure of any Confidential Information concerning
                                            such matters and so that these obligations shall continue to apply during the term of this
                                            Agreement and for a period of 5 years thereafter but shall cease to apply to information
                                            which shall come into the public domain other than by a breach of this Section 8.



 


		8.2.	No
                                            announcement or publicity concerning the terms of this Agreement shall be made or issued
                                            by any of the Parties hereto without the prior written approval of the other Party other
                                            than as required by Law or by the rules of any regulatory organisation to which any of the
                                            Parties hereto is subject (in which case the Parties shall consult with each other on the
                                            form of the announcement if possible under time and legal constraints).



 


		8.3.	Both
                                            Parties consider the restrictions comprised in this clause 8 to be reasonable and the provisions
                                            herein shall remain in force and be fully applicable in all circumstances in accordance with
                                            its terms and in particular shall not be discharged or affected by any breach or repudiation
                                            of this Agreement in each case whatever its nature or howsoever caused or arising or by any
                                            other matter, circumstance, or thing whatsoever.



 









    9


    


    

 





	9.	Term
                                            and Termination



 


		9.1.	This
                                            Agreement shall be in effect for an unlimited period of time until terminated by either Party
                                            in accordance with the provisions of this Section 9 (the “Term”):



 


		9.2.	This
                                            Agreement may be terminated at any time by either party upon delivering to the other arty
                                            a prior written notice of at least 90 days.



 


		9.3.	This
                                            Agreement may be terminated by written notice of at least 7 days as a result of a breach
                                            of the provisions of this Agreement committed by a Party which was not cured within 7 days
                                            as of receipt of notice from the non-breaching party.



 


		9.4.	Clauses
                                            4, 5, 6, 8, 9, 10 and 11 shall survive the termination of this Agreement for any reason whatsoever.



 


	10.	General



 


		10.1.	This
                                            Agreement shall be governed and enforced exclusively in accordance with the laws of the state
                                            of Israel in all respects including its construction, interpretation and performance and
                                            without regard to its conflict of laws rules and policies. It is hereby agreed that in the
                                            event of a dispute arising in connection with this Agreement the parties shall first try
                                            to resolve the dispute by a meeting and a discussion between the CEOs of both parties. If
                                            the parties fail to amicably resolve the dispute within 14 days of commencement of such discussions,
                                            each party may refer the dispute to the authorized courts of Tel Aviv, Israel, which shall
                                            have exclusive jurisdiction over all disputes arising in connection with this Agreement.



 


		10.2.	This
                                            Agreement supersedes all prior discussions, agreements, and writings and constitutes the
                                            entire agreement between the Parties with respect to the subject matter hereof.



 


		10.3.	No
                                            waiver or modification of this Agreement will be binding upon any party unless made in writing
                                            and signed by a duly authorized representative of such party and no failure or delay in enforcing
                                            any right will be deemed a waiver.



 


		10.4.	None
                                            of the Parties hereto may assign its rights or obligations under this Agreement, in whole
                                            or in part, without the prior written consent of the other Party hereto.



 


		10.5.	In
                                            no event shall either party be liable to the other Party for any consequential, incidental,
                                            special or indirect damages, however caused, arising out of or in connection with this Agreement,
                                            or of any other obligations relating to this Agreement, whether or not the Party has been
                                            advised of the possibility of such damages, unless such damages are a result of wilful misconduct
                                            or gross negligence of the damaging party.



 


		10.6.	Nothing
                                            in this Agreement shall constitute or be deemed to constitute a partnership or principal
                                            and agent relationship between the Parties hereto and neither of them shall have any authority
                                            to bind the other in any way.



 


		10.7.	Any
                                            right or remedy of the Parties in respect of a breach of any provision of this Agreement
                                            shall be in addition and without prejudice to all other rights and remedies of the Parties,
                                            and no failure to exercise or delay in exercising or enforcing any right or remedy shall
                                            operate to impair or constitute a waiver by that Party of that or any of its other rights
                                            or remedies and no single or partial exercise or enforcement of any such right or remedy
                                            shall preclude or restrict any other or further exercise or enforcement of any such right
                                            or remedy.






 







		10.8.	If
                                            any of the provisions of this Agreement is held to be invalid, illegal or unenforceable in
                                            any respect under any law, the validity, legality and enforceability of the remainder of
                                            this Agreement shall not be affected.



 


		10.9.	A
                                            notice given under this Agreement shall be in writing in the English language and shall be
                                            sent for the attention of the party, and to the address, electronic address or fax number,
                                            given in the preamble to this Agreement and/or notified in writing to the other party, and
                                            shall be delivered personally, sent by fax or sent by electronic mail.



 


		10.10.	A
                                            notice is deemed to have been received if delivered personally, at the time of delivery,
                                            in the case of fax or electronic mail, on the next business day following the day of transmission.



 






    10


    


    

 


In
Witness Whereof, the Parties have caused this Agreement to be executed and become effective on the Effective Date.


 


	/s/
    Tomer Izraeli	 	Dr.
    Lior Shaltiel
	Polyrizon
    Ltd. 	 	NurExone
    Biologic Ltd.
	 	 	 
	By: 	Tomer Izraeli, CEO	 	By: 	Dr. Lior Shaltiel, CEO 


 






    11


    


    

 


 


 


ANNEX
A





 


 


 


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-374012


 



    


    


    







 





 


Nasal
spray


Formulation
development and technical batch preparation in view of pre-clinical studies


 


POLYRIZON
LTD


Send
to: NUREXONE


Contact
person: Dr. Lior Shaltiel


Email:lior@nurexone.com


24th
of May 2022


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 



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Work
plan proposal


 


Background:


 


 1. Trap & Target drug delivery technology for intranasal administration




 


The
nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. Each cavity is the continuation of one
of the two nostrils. The nasal cavity is the uppermost part of the respiratory system and provides the nasal passage for inhaled air
from the nostrils to the nasopharynx and rest of the respiratory tract. The nasal mucosa, also called respiratory mucosa, lines the entire
nasal cavity, from the nostrils to the pharynx. A dynamic layer of mucus overlies the nasal epithelium (the outermost layer of cells
of the nasal mucosa).


 


The
nasal sub-mucosa underlies the basement membrane. This layer is made up of glands which secrete watery substances and mucus, nerves,
an extensive network of blood vessels and cellular elements like blood plasma. The entire mucosa is highly concentrated with blood vessels
and contains large venous-like spaces.


 








 


Figure
1: Schematic illustrations of the mucosal tissue (left) and nasal cavity anatomy (right).


 


The
term ‘mucoadhesion’ refers to the adhesion of specific polymers to the surface of the mucosal layer. The mucosal layer is
made up of mucus, a viscoelastic fluid, which is secreted by the epithelial cells. A mucoadhesion polymer helps to promote the adhering
of a given formulation to the nasal mucosa by physically interacting with the mucosa. Various properties impact the mucoadhesive of polymers,
such as: (i) molecular weight; (ii) chain length; (iii) viscosity; (iv) degree of cross-linking; (v) spatial conformation; (vi) flexibility
of polymer chains; (vii) concentration; (viii) charge and degree of ionization – anion>cation>non-ionic; (ix) degree of hydration;
and (x) pH.


 


The
mechanism of mucoadhesion is characterized by to two steps: contact stage and consolidation stage. The first contact stage is
characterized by the initial contact between the polymers and the mucous membrane, with spreading and initiating a deep contact with
the mucus layer. In the second consolidation step, the polymers are activated by the presence of moisture and as they hydrate they
become mucoadhesive.


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 






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Advantages
of intranasal drugs delivery


 


The
nasal cavity is an important target for local and systemic drug administration as well as targeting the central nervous system. Due to
highly vascularization of the nasal mucosa, liquids or particles that attach to this surface can act either locally or be absorbed into
the bloodstream. In addition, the first cranial nerve, or olfactory nerve, is the only point where the central nervous system is exposed
to the body’s mucosa, and it is one of six nerves that branch into the nose cavity. This means that medications can be absorbed
directly into the brain, bypassing the blood-brain barrier.


 








 


Figure
2: Intranasal drug delivery and potential uptake routes


 


Although
there are many advantages for delivering medicines intranasally, there are also a few drawbacks, such as quick evacuation from the nasal
canal, limited bioavailability, and difficulty getting a big enough dosage due to the limited absorption area. Our T&T technology
is developed to address the abovementioned drawbacks to further improve the efficiency of intranasal administration.


 


The
T&T platform delivery technology consist of a mucoadhesive polymers mixture designed to allow a long residence time and an intimate
contact with the mucosal tissue for potentially improved delivery of medicines. The T&T platform can be tailored for different molecules
to address their specific challenges thus believed to induce improved therapeutic effect. The T&T technology has been designed to
enable mucoadhesion and prolonged retention at the deposition site by tailoring the physicochemical properties through composition, concentration
and crosslinking of the key polymers of the formulation appears pivotal for the potential development as nasal medicinal product candidates.


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 




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2. Project scope




 


NurExone
Biologic Ltd is developing biological extracellular vesicles (EV)-based technology drug platform to treat damage in the Central Nerve
System (CNS).


 


Following
small animal proof of concept, Nurexone wishes to develop a formulation to potentially improve the intranasal drug delivery.


 


Nurexone
requires Polyrizon Ltd. to develop an intranasal formulation, conduct analytical development and to produce technical batch (non-GMP)
in the scope of pre-clinical studies in Israel.


 


	API
    / Drug Substance	Loaded
    exosomes (exosomes + siRNA)
	Dosage
    form	Nasal
    solution (non-sterile) Assuming low viscosity
	*********	*********
	Primary
    packaging	TBD
    if relevant
	Storage
    (temp. and biological

    contaminations)
	15-25°C
	Development
    phase	Pre-clinical
	Destination	Israel
	Safety
    data	TBD
	Batch
    size	TBD
    if necessary
	Timelines
    Beginning of work	Q2-Q3
    2022


 


MSDS
of active ingredient(s) should be provided by Nurexone. This offer assumes compounds are classified maximum OEB3 and will be safe to
handle within the standard safety precautions of Polyrizon Ltd. If not, they will be handled as if it was a highly potent and the current
proposal may need to be revised.


 


All
formulation, manufacturing and analytical data at disposal of Nurexone will be shared with Polyrizon.


 


The
sourcing of raw materials (active compounds and excipients, GMP grade to be provided for clinical production) will be discussed between
Polyrizon Ltd. and Nurexone (cost for purchase and shipments are not included).


 


Associated
documentation should be provided.


 


The
supply of primary packaging items (vials with spray pump cap) will be discussed between Polyrizon Ltd. and Nurexone (cost for purchase
not included). Nurexone remains responsible for the choice of packaging supplier, in case needed.


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 





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1st
part: *********


			1. *********



			2. *********



		a.	*********



			i.
                                            *********



			ii.
                                            *********



			iii. *********



		b.	*********



		c.	*********



		d.	*********



			3. *********



 


1st
part deliverables:


		1.	*********



		2.	*********



 


_____________________________________________________________________


 


2nd
part: *********


1.
   *********


		a.	*********



		i.	*********



		b.	*********



		c.	*********



 


2nd
part deliverables:


		1.	*********



		2.	*********



 


_____________________________________________________________________



 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 





    A-5


     


    

 





 



3rd
part: *********


*********


 


3rd
part deliverables:


*********


_____________________________________________________________________


 


4th
part: *********


*********


 


4th
deliverables:


*********


 


5th
part: *********


*********





_____________________________________________________________________


5th
part deliverables:


*********


 


_____________________________________________________________________


 



Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 





    A-6


     


    

 





 



6th
part: *********


*********


		●	*********



		i.	*********



		ii.	*********



		●	*********



			iii. *********



			iv. *********



			v. *********



			vi. *********



			vii. *********



			viii. *********



 


6th
part deliverables:


1.
*********





_____________________________________________________________________


 


7th
part: *********


 


*********


_____________________________________________________________________


 



Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120


 





    A-7


     


    

 





 



Project
estimated timelines:


 


Starting
date: Q2 or Q3 2022, to be confirmed at approval of offer.


 


Estimated
timelines below are indicative only. A planning will be provided at approval of offer. T0 is at receipt of materials from Nurexone (exosomes).


 


	Estimated
    time lines	Weeks
    No.
	 	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32
	Part
    #1 - Vehicle development	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Part
    #2 - Formulation characterization	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Part
    #3 - Permeability assays	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Part
    #4 - Nasal deposition studies	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Part
    #5 - Preservative selection	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Part
    #6 - Stability	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 


 


Financial
proposal


 


Price
calculation:


 


	Program
    description	Cost
    Euros Taxes excluded
	*********	*********
	*********	*********
	*********	*********
	*********	*********
	*********	*********
	*********	*********
	*********	*********
	 
	*********	*********


 


Payment
schedule:


 


		●	*********



 


		●	*********



 


		●	*********



 


It
is hereby agreed that in the event the actual cost of a Work Order will substantially deviate from the agreed upon budget, the Parties
will discuss such a matter in good faith between them


 


	/s/ Tomer Izraeli	 	/s/ Dr. Lior Shaltiel
	Tomer Izraeli, CEO	 	Dr. Lior Shaltiel, CEO
	Polyrizon Ltd. 	 	NurExone Biologic



 


 


Polyrizon Ltd. - Address: HaTidhar St.
5 Raanana Israel


Mail: info@polyrizon-biotech.com
- Phone: +972-9-3740120

 





A-8