EXHIBIT 10.2


 


 





 


Dated 04
February 2014


 


Kitov Pharmaceutical
Limited


 


AND


 


Java Clinical
Research Limited


 


Master Research
Services Agreement


Strictly
Confidential


 




    	 



    	 



    

 


THIS MASTER
SERVICES AGREEMENT (this “AGREEMENT”)


 


BETWEEN:


 


		(1)	Kitov
                                         Pharmaceuticals Limited (“Kitov”) a Company incorporated in Israel and
                                         whose principal place of business and resgistered address is at, 11 Bet Hadfus Street
                                         Jerusalem 95483, Israel.



		(2)	JAVA CLINICAL RESEARCH
LIMITED, a company incorporated in Ireland, registered number 311398, with registered office address 2 Grand Canal Square,
Dublin 2, Fitzwilliam Business Centre, 26/27 Upper Pembroke Street, Dublin 2 ("JAVA");



(each
a "Party" and together the "Parties").


 


RECITALS


 


		(A)	The
                                         Sponsor is concerned with the diagnosis, treatment and prevention of disease and clinical
                                         research for the improvement of healthcare. JAVA is in the business of providing research
                                         services; and



 


		(B)	The
                                         Sponsor and JAVA desire to enter into this Agreement to provide the terms and conditions
                                         upon which the Sponsor may engage JAVA from time-to-time to provide research services
                                         for individual projects by executing individual Work Orders (as defined below) specifying
                                         the details of the services and the related terms and conditions.



 


NOW, IT
IS HEREBY AGREED AS FOLLOWS in consideration of the mutual covenants contained herein:


 


		1.	DEFINITIONS



 


		1.1.	"Applicable
                                         Laws" shall mean all laws, rules and regulations including without limitation,
                                         Good Clinical Practice (“GCP”) that are applicable to the performance by
                                         JAVA of the Services under this Agreement.



 


		1.2.	"Change
                                         Order" shall have the meaning given to the term in Clause 2.3.



 


		1.3.	"Claims"
                                         shall mean all and any claims (whether successful or otherwise), loss, liability, damages
                                         and expenses, including reasonable attorneys' fees and expenses and legal costs.



 


		1.4.	"Confidential
                                         Information" shall mean all confidential and proprietary information, including
                                         without limitation, inventions, specifications, designs, know-how, trade secrets, inventions
                                         (including patent applications covering such inventions), data, information, and any
                                         improvements, modifications, derivations, or compilations thereto that is owned, licensed
                                         by or controlled by the disclosing Party; provided however, that Confidential Information
                                         shall not include any information which is:



 


		1.4.1.	already
                                         known to the receiving Party at the time of disclosure, as evidenced by such Party's
                                         written records, provided such information was not obtained directly or indirectly by
                                         the receiving Party from the disclosing Party pursuant to a confidentiality agreement;



 


		1.4.2.	publicly
                                         known prior to or after disclosure, through no default of the receiving Party;



 


		1.4.3.	disclosed
                                         in good faith to the receiving party by a third party, lawfully and contractually entitled
                                         to make such disclosure; or



 




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		1.4.4.	is
                                         independently discovered without the aid or application of the Confidential Information
                                         as shall be evidenced by the written records of the receiving Party.



 


		1.5.	"Effective
                                         Date" shall mean the date of this Agreement.



 


		1.6.	“GCP”
                                         shall mean the ICH Harmonised Tripartite Guidelines for Good Clinical Practice, and
                                         any subsequent versions thereof.



 


		1.7.	"Intellectual
                                         Property Rights" shall mean all patents, patent applications, copyrights, copyright
                                         applications, trademarks, trade secrets, know-how and other intellectual property rights.



 


		1.8.	"Materials"
                                         shall have the meaning given to the term in Clause 3.1.



 


		1.9.	"Project"
                                         shall have the meaning given to the term in Clause 2.1.1.



 


		1.10.	"Services"
                                         shall have the meaning given to the term in Clause 2.2.2.



 


		1.11.	"Term"
                                         shall have the meaning given to the term in Clause 12.1.



 


		1.12.	"Work
                                         Orders" shall have the meaning given to the term in Clause 2.2.1.



 


		2.	SCOPE
                                         OF THE AGREEMENT, WORK ORDERS AND CHANGE ORDERS



 


		2.1.	Scope
                                         of Agreement and Performance of the Services



 


		2.1.1.	This
                                         Master Agreement allows the Parties to contract for multiple projects and other services
                                         requested by the Sponsor and agreed by JAVA (each a "Project") through
                                         the issuance of multiple Work Orders in accordance with the terms of this Agreement.



 


		2.2.	Work
                                         Orders



 


		2.2.1.	The
                                         specific details of each Project under this Agreement shall be separately negotiated
                                         and agreed by the Parties and specified in writing in substantially the form attached
                                         hereto in Appendix 1 (each a "Work Order").



 


		2.2.2.	Each
                                         Work Order will include details of the services to be provided by JAVA (“Services”),
                                         scope of work, timelines, budget and payment schedule.



 


		2.2.3.	Each
                                         Work Order, upon execution, shall be incorporated into this Agreement and shall be subject
                                         to all of the terms and conditions of this Agreement, in addition to the specific details
                                         set forth in the Work Order.



 


		2.2.4.	To
                                         the extent any terms or provisions of a Work Order conflict with the terms and provisions
                                         of this Agreement, the terms and provisions of this Agreement shall prevail, except to
                                         the extent that the applicable Work Order expressly and specifically states an intent
                                         to supersede the Agreement on a specific matter and such Work Order is signed by both
                                         Parties.



 




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		2.3.	Change
                                         Orders



 


		2.3.1	Any
                                         material change in the details of a Work Order, or the assumptions upon which the Work
                                         Order is based, shall require written amendment to the Work Order in substantially the
                                         form attached hereto in Appendix 2 (a "Change Order").



 


		2.3.2	Each
                                         Change Order shall detail the requested changes to the applicable task, responsibility,
                                         duty, budget, timeline or other matter.



 


		2.3.3	The
                                         Change Order will become effective upon the execution of the Change Order by both Parties.



 


		2.3.4	Both
                                         Parties agree to act in good faith and promptly when considering a Change Order requested
                                         by the other Party.



 


		2.4	Services



 


		2.4.1	JAVA
                                         shall perform the Services in good faith, with due care and skill, in accordance with
                                         the terms of this Agreement, the reasonable instructions of the Sponsor, and with all
                                         Applicable Laws.



 


		2.4.2	The
                                         Sponsor agrees to cooperate with JAVA and provide JAVA with such information and assistance
                                         as JAVA may reasonably require in order to enable or facilitate JAVA duly and punctually
                                         to comply with its obligations under this Agreement and each Work Order.



 


		2.4.3	Except
                                         as expressly stated in this Agreement, all warranties, conditions and terms, whether
                                         express or implied by statute, common law or otherwise (including but not limited to
                                         fitness for purpose and suitability) are hereby excluded to the extent permitted by law.



 


		3.	MATERIALS



 


		3.1	The
                                         Sponsor shall provide JAVA with materials required for the purpose of performing the
                                         Projects (the "Materials").



 


		3.2	JAVA
                                         undertakes that it shall not:



 


		3.2.1	use
                                         the Materials other than for the purpose of performing the Projects;



 


		3.2.2	make
                                         the Materials available to any third party;



 


		3.2.3	allow
                                         access to the Materials by any of its employees or students except those who are directly
                                         involved in performing the Projects;



 


		3.2.4	make
                                         any commercial use of the Materials or any composition made using the Materials; or



 


		3.2.5	analyse
                                         or otherwise attempt to determine the composition of the Materials.



 


		3.3	The
                                         Sponsor warrants that all Materials shall be fit for purpose as envisaged by this Agreement
                                         and that all such Materials may be lawfully used in conducting the Services.



 




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		3.4	Upon
                                         termination of the Agreement, any unused Materials shall, at the Sponsor's option, either
                                         be destroyed by JAVA or returned to the Sponsor, at the Sponsor’s expense.



 


		4.	PAYMENT
                                         OF FEES AND EXPENSES



 


		4.1.	The
                                         fees to be charged by JAVA for each Project performed hereunder (the "Service
                                         Fees") shall be set out in the relevant Work Order.



 


		4.2.	In
                                         consideration of the supply of Services for each Project, the Sponsor shall pay JAVA
                                         the Services Fees and reasonable and necessary vouched expenses incurred in the performance
                                         of the Services as set out in the Work Order on the following basis:



 


		4.2.1.	the
                                         Service Fees and the total cost of each Project and an estimate of the total expenses
                                         to be incurred in relation thereto (the "Total Project Cost") shall
                                         be set out in the relevant Work Order; and



 


		4.2.2.	in
                                         no event shall the Sponsor be required to pay any amount exceeding the Total Project
                                         Cost unless otherwise agreed in writing by both Parties by Change Order(s) (as specified
                                         in Clause 2.3 above).



 


		4.2.3.	Invoices
                                         for fees and expenses shall be issued on a monthly basis and Sponsor shall pay each invoice
                                         within 30 days of receipt.



 


		4.3.	All
                                         sums referred to in each Work Order shall be exclusive of Value Added Tax (VAT). The
                                         Sponsor shall pay all VAT at the rate and in the manner prescribed by law from time to
                                         time.



 


		5.	PERSONNEL



 


		5.1.	JAVA
                                         shall be responsible for ensuring that all personnel which it assigns to each Project
                                         are fully qualified by education, training and experience to perform their respective
                                         obligations under this Agreement and the relevant Work Order ("JAVA Personnel").



 


		5.2.	JAVA
                                         shall remain fully liable for the performance by all JAVA Personnel of JAVA’s obligations
                                         hereunder.



 


		5.3.	The
                                         Sponsor shall be responsible for ensuring that all personnel which it assigns to each
                                         Project (“Sponsor Personnel") are fully qualified by education, training
                                         and experience to perform their respective obligations under this Agreement and the relevant
                                         Work Order.



 


		5.4.	The
                                         Sponsor shall remain fully liable for the performance by all Sponsor Personnel of the
                                         Sponsor’s obligations hereunder.



 


		6.	CONFIDENTIAL
                                         INFORMATION/ANNOUNCEMENTS



 


		6.1.	During
                                         the Term and for a period of 7 (seven) years thereafter, each Party undertakes to maintain
                                         as confidential all Confidential Information disclosed by the other Party to it (the
                                         “Confidential Information") before or after the date of this Agreement.



 


		6.2.	Each
                                         Party shall not without the other Party’s prior written consent:



 


		6.2.1.	use
                                         the Confidential Information for any purpose other than the proper performance of the
                                         Services; or



 




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		6.2.2.	disclose
                                         the Confidential Information to any other person, save those employees, representatives
                                         and agents as may be strictly necessary in order to perform the Services, and provided
                                         that JAVA first ensures that such person is under a duty of confidentiality to JAVA to
                                         protect the Sponsor’s Confidential Information on no less onerous terms than as
                                         set out in this Clause 6.



 


		6.3.	Notwithstanding
                                         the provisions of this Clause 6, Confidential Information may be disclosed to the extent
                                         required by law or as ordered by a court or other regulatory body having competent jurisdiction,
                                         provided that if a Party becomes legally required to disclose any Confidential Information
                                         hereunder, the receiving Party shall give the disclosing Party prompt notice of such
                                         requirement to enable the disclosing Party to seek a protective order or other appropriate
                                         remedy concerning any such disclosure. The receiving Party shall fully co-operate with
                                         the disclosing Party in connection with the disclosing Party’s efforts to obtain
                                         any such order or other remedy. If any such order or other remedy does not fully preclude
                                         disclosure, the receiving Party shall make such disclosure only to the extent that such
                                         disclosure is legally required. JAVA acknowledges that Sponsor is a publicly traded corporation
                                         and is subject to certain reporting obligations under any applicable laws, and hence
                                         JAVA agrees Sponsor has a right to make such publications as required under any such
                                         applicable laws.



 


		6.4.	JAVA
                                         agrees to maintain, as strictly confidential the subject matter of this Agreement and
                                         the fact that the Parties have entered into this Agreement.



 


		6.5.	Upon
                                         termination or expiration of this Agreement, JAVA shall promptly return, or at the Sponsor's
                                         request, destroy all of the Sponsor's Confidential Information.



 


		6.6.	Each
                                         Party shall be entitled to provide a copy of this Agreement (and any related documents)
                                         to a potential third-party acquirer, investor, or other commercialisation partner, provided
                                         that the relevant third party has entered into a confidentiality agreement with the disclosing
                                         Party on terms equivalent hereto.



 


		6.7.	In
                                         relation to all personal data (as defined in the Data Protection Acts 1988 and 2003 as
                                         amended), the Parties shall at all times comply with the Data Protection Acts 1988 and
                                         2003 as amended, and the Parties shall only undertake processing of personal data reasonably
                                         required in connection with the Services and in compliance with law.



 


		6.8.	JAVA
                                         acknowledges that information provided by it to the Sponsor may be the subject of a request
                                         under the Freedom of Information Act, 1997 (“FOI”), as amended. If a request
                                         is made under FOI, the Sponsor shall give JAVA prompt notice of such request to enable
                                         JAVA to seek a protective order or other appropriate remedy concerning any such disclosure.
                                         The Sponsor shall fully co-operate with JAVA in connection with JAVA's efforts to obtain
                                         any such order or other remedy. If any such order or other remedy does not fully preclude
                                         disclosure, the Sponsor shall make such disclosure only to the extent that such disclosure
                                         is legally required.



 


		7.	PROJECT
                                         RESULTS, INTELLECTUAL PROPERTY RIGHTS AND REPORTS



 


		7.1.	JAVA
                                         agrees that:



 


		7.1.1.	all
                                         data, materials and reports, and all rights therein (the "Project Results");
                                         and



 




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		7.1.2.	all
                                         Intellectual Property Rights (the "Project IP");



 


conceived,
created, developed and or otherwise invented as a result of performing the Services shall be owned exclusively by the Sponsor.


 


		7.2.	JAVA
                                         shall assign to the Sponsor all right, title and interest in and to all Project Results
                                         and Project IP and further agrees to execute all such documents, make such applications,
                                         give such assistance and do such acts and things as may be necessary or desirable to
                                         vest in and register or obtain letters patent in the name of the Sponsor and otherwise
                                         to protect and maintain such Project Results and Project IP.



 


		7.3.	JAVA
                                         shall promptly disclose all Project Results and Project IP to the Sponsor and provide
                                         copies of all documents relating to same to the Sponsor at its request at any time during
                                         or after the Term.



 


		7.4.	JAVA
                                         has informed the Sponsor that JAVA possesses certain processes, know-how, trade secrets
                                         and other intellectual assets relating to applicable processing, laboratory analyses,
                                         analytical methods, procedures and techniques, computer technical expertise and software
                                         which have been developed by JAVA prior to the Effective Date and which the Sponsor understands
                                         are applied and utilised by JAVA on an ongoing basis in providing services to clients
                                         (collectively "JAVA Property"). JAVA and the Sponsor agree that the
                                         JAVA Property or any improvements relating to the JAVA Property developed by JAVA pursuant
                                         to this Agreement shall be owned exclusively by JAVA.



 


		7.5.	Subject
                                         to Clause 11, JAVA shall not, without the prior written consent of the Sponsor, disclose
                                         or publish any Project Results or Project IP, or use any Project Results or Project IP
                                         for any purpose other than to perform its obligations hereunder.



 


		7.6.	Reports
                                         and Record Retention



 


		7.6.1.	JAVA
                                         will provide reports in writing on the Services performed (each a "Report")
                                         on a regular basis.



 


		7.6.2.	If
                                         for any reason any Report is not to the satisfaction of the Sponsor acting reasonably,
                                         JAVA shall re-produce such Report to the satisfaction of the Sponsor.



 


		7.6.3.	JAVA
                                         shall maintain all books, records, data, reports, pictures and other documents (both
                                         in electronic and paper form) relating to the Services (the "Records")
                                         for the maximum period required by law (the "Retention Period"). The
                                         Parties agree that all Records shall constitute Sponsor Confidential Information and
                                         the provisions of Clause 6 (Confidentiality) shall apply to all such Records. Upon expiry
                                         of the Retention Period, JAVA shall provide all original Records (both in electronic
                                         and paper form), and all copies thereof, to the Sponsor.



 


		8.	SOPS/REGULATORY
                                         INSPECTIONS



 


		8.1.	Upon
                                         the written request of the Sponsor, JAVA shall provide the Sponsor with a list of all
                                         of JAVA's standard operating procedures ("SOPs") relevant to the Services
                                         to be performed by JAVA hereunder.



 


		8.2.	At
                                         any time during the Term, JAVA shall allow the Sponsor to review all such SOPs, including
                                         any updates thereof, on JAVA's premises.



 




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		8.3.	If
                                         any regulatory agency requests to inspect any books, records, or facilities of JAVA,
                                         relating to the Services, JAVA shall immediately notify the Sponsor (within 1 business
                                         day) and shall promptly notify the Sponsor of the outcome of any such inspection within
                                         5 business days of such outcome becoming known to Service Provider.



 


		9.	REPRESENTATIONS,
                                         WARRANTIES AND COVENANTS



 


		9.1.	JAVA
                                         represents and warrants to the Sponsor that the performance by JAVA of its obligations
                                         hereunder are not inconsistent with and will not breach any third-party obligations.



 


		9.2.	JAVA
                                         covenants that it shall have agreements in place with all servants and agents, that impose
                                         confidentiality obligations on such servants and agents, vest in JAVA any rights such
                                         servants and agents might otherwise have in any Project Results or Project IP, permit
                                         JAVA to assign all such rights to the Sponsor, and otherwise enable JAVA to comply with
                                         the terms of this Agreement and any Work Order hereunder, including without limitation
                                         any timeline set out therein.



 


		10.	INDEMNIFICATION/LIABILITY



 


		10.1.	The
                                         Sponsor shall indemnify and hold harmless JAVA and its employees, agents, officers and
                                         directors from and against any Claims incurred or sustained by JAVA arising out of the
                                         Services performed under this Agreement, except to the extent such Claims arise out of,
                                         or are connected with any:



 


		10.1.1.	breach
                                         of any representation, covenant, warranty or obligation by JAVA under this Agreement;
                                         or



 


		10.1.2.	negligent
                                         act or omission or wilful misconduct on the part of JAVA or any of its agents or employees
                                         in the performance of this Agreement.



 


		10.2.	JAVA
                                         shall indemnify and hold harmless the Sponsor and their respective employees, agents,
                                         officers and directors from and against any Claims incurred or sustained by the Sponsor
                                         arising out of or in connection with any:



 


		10.2.1.	breach
                                         of any representation, covenant, warranty or obligation by JAVA under this Agreement;
                                         or



 


		10.2.2.	negligent
                                         act or omission or wilful misconduct on the part of JAVA or any of its respective employees,
                                         agents, officers and directors in the performance of this Agreement.



 


		10.3.	The
                                         Party seeking an indemnity shall:



 


		10.3.1.	fully
                                         and promptly notify the other Party of any claim or proceedings, or threatened claim
                                         or proceedings;



 


		10.3.2.	permit
                                         the indemnifying Party to take full control of such claim or proceedings, with counsel
                                         of the indemnifying Party's choice, provided that the indemnifying Party shall reasonably
                                         and regularly consult with the Party seeking to be indemnified in relation to the progress
                                         and status of such claim or proceedings;



 


		10.3.3.	co-operate
                                         in the investigation and defence of such claim or proceedings; and



 




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		10.3.4.	take
                                         all reasonable steps to mitigate any loss or liability in respect of any such claim or
                                         proceedings.



 


Neither
the indemnifying Party nor the Party seeking to be indemnified shall acknowledge the validity of, compromise or otherwise settle
any Claim without the prior written consent of the other, which shall not be unreasonably withheld.


 


The
Parties agree that the aggregate liability of either party to the other party under or in connection with this Agreement shall
in no event exceed the total Service Fees paid by the Sponsor to JAVA under this Agreement, provided however, that this limitation
to each other shall not apply to the indemenities set forth in 10.1 and 10.2 hereunder .


 


		10.4.	NOTWITHSTANDING
                                         ANYTHING TO THE CONTRARY IN THIS AGREEMENT, THE SPONSOR AND JAVA SHALL NOT BE LIABLE
                                         TO THE OTHER BY REASON OF ANY REPRESENTATION OR WARRANTY, CONDITION OR OTHER TERM OR
                                         ANY DUTY OF COMMON LAW, OR UNDER THE EXPRESS TERMS OF THIS AGREEMENT, FOR ANY CONSEQUENTIAL,
                                         SPECIAL OR INCIDENTAL OR PUNITIVE LOSS OR DAMAGE (WHETHER FOR LOSS OF CURRENT OR FUTURE
                                         PROFITS, LOSS OF ENTERPRISE VALUE OR OTHERWISE) AND WHETHER OCCASIONED BY THE NEGLIGENCE
                                         OF THE RESPECTIVE PARTIES, THEIR EMPLOYEES OR AGENTS OR OTHERWISE.



 


		10.5.	Nothing
                                         in this Agreement shall limit the liability of either Party for fraud, or limit the liability
                                         of either Party to any third party under applicable laws where any act or omission of
                                         either Party results in death or personal injury.



 


		10.6.	Insurance
                                         



 


JAVA
shall furnish certificates of insurance evidencing the required insurance policies to the Sponsor as soon as practicable after
the Effective Date and within 30 days after renewal of such policies.


 


		11.	PUBLICATION



 


		11.1.	It
                                         is acknowledged and agreed by JAVA that:



 


		11.1.1.	publication
                                         of the Project Results and/or Project IP in whole or in part shall be within the sole
                                         and absolute discretion of the Sponsor;



 


		11.1.2.	JAVA
                                         shall not publish or refer to any Project Results and/or Project IP, in whole or in part,
                                         without the prior written consent of the Sponsor; and



 


		11.1.3.	JAVA
                                         will not use the Sponsor’s name in connection with any publication or promotion
                                         without the Sponsor’s prior written consent.



 


		11.2.	In
                                         the event that such consent is given, prior to publication or communication of any Project
                                         Results and/or Project IP by JAVA, JAVA shall provide to the Sponsor, for its review
                                         and comment, a copy of the relevant abstract, presentation, or paper 30 days before such
                                         abstract, presentation, or paper is submitted for publication.



 


		11.3.	No
                                         release of such abstract, presentation, or paper shall be permitted without the prior
                                         written consent of the Sponsor.



 


		11.4.	The
                                         provisions of this Clause 11 also apply to any amendments that are subsequently requested
                                         by referees or journal editors.



 




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		12.	TERM
                                         and TERMINATION



 


		12.1.	This
                                         Agreement shall commence on the Effective Date and shall continue until terminated by
                                         either Party in accordance with this Clause 12 (the "Term").



 


		12.2.	This
                                         Agreement or any Work Order may be terminated without cause by either Party at any time
                                         during the term of the Agreement on sixty (60) days prior written notice to the other
                                         Party. The written termination shall identify whether this Agreement or a specific Work
                                         Order or Work Orders are being terminated.



 


		12.3.	In
                                         addition to the rights of termination provided for elsewhere in this Agreement, each
                                         Party shall be entitled forthwith to terminate this Agreement by written notice to the
                                         other Party if:



 


		12.3.1.	either
                                         Party commits any material breach of any provisions of this Agreement, and in the case
                                         of a breach capable of remedy, fails to cure the same within 30 days after receipt of
                                         a written notice giving full particulars of the breach and requiring it to be cured;
                                         or



 


		12.3.2.	either
                                         Party goes into liquidation (except for the purposes of amalgamation or reconstruction
                                         and in such manner that the company resulting therefrom effectively agrees to be bound
                                         by or assume the obligations imposed on such party under this Agreement); or



 


		12.3.3.	an
                                         encumbrancer takes possession or a receiver is appointed over any of the property or
                                         assets of either Party; or



 


		12.3.4.	a
                                         Party becomes unable to pay its debts as and when they fall due or is deemed to be unable
                                         to pay its debts as they fall due; or



 


		12.3.5.	any
                                         proceedings are filed or commenced by any Party under bankruptcy, insolvency or debtor
                                         relief laws.



 


		12.4.	Upon
                                         receipt of a termination notice from the Sponsor, JAVA shall cease performing any work
                                         not necessary for the orderly close out of the affected Projects or for the fulfilment
                                         of regulatory requirements.



 


		12.5.	In
                                         the event of termination of this Agreement or any Work Order, each Party will co-operate
                                         in good faith with the other Party to wind-down and terminate or transition, at Sponsors 
                                         discretion, to another service provider, any Services then in progress that are affected
                                         by such termination and will perform such additional acts as are reasonably necessary
                                         in order to effect such wind-down or transition of the Services.  JAVA will provide
                                         to SPONSOR within forty-five (45) days following any Work Order termination date, an
                                         accounting for all Services performed together with reasonable supporting documentation. 
                                         SPONSOR will promptly review such accounting and will notify JAVA in writing of its approval
                                         or will notify CRO of any disputed amounts.  SPONSOR will pay CRO within 30 days
                                         after receipt of the approved accounting or upon mutual agreement of the final amount
                                         due for: (1) all unpaid and undisputed amounts for Services rendered and expenditures
                                         made by JAVA in accordance with this Agreement and the applicable Work Order prior to
                                         the Termination Date; and (2) expenses resulting from reasonable non-cancellable obligations
                                         that JAVA properly incurred for the Services in accordance with a Work Order prior to
                                         receipt of notice of termination and which JAVA used commercially reasonable efforts
                                         to cancel after receipt of notice of termination.



 




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		12.6.	Upon
                                         the termination of this Agreement or any Work Order, JAVA shall deliver to the Sponsor
                                         all Confidential Information and Materials provided by the Sponsor to JAVA for the conduct
                                         of Services under the terminated Work Orders, and JAVA shall also deliver to the Sponsor
                                         all Project IP, Project Results and any other data, information and documentation produced
                                         as the result of Services performed by JAVA under the terminated Work Orders.



 


		13.	MISCELLANEOUS



 


		13.1.	This
                                         Agreement shall be governed by and construed in accordance with Irish laws and, subject
                                         to Clauses 13.2 and 13.3, the Parties submit to the exclusive jurisdiction of the Irish
                                         courts.



 


		13.2.	Resolution
                                         of Disputes: The Parties shall attempt in good faith to resolve promptly any dispute
                                         arising out of or relating to this Agreement by negotiation. If the matter cannot be
                                         resolved in the normal course of business either Party may give the other Party written
                                         notice of any such dispute not resolved, after which the dispute shall be referred to
                                         more senior executives of both Parties, who shall likewise attempt to resolve the dispute.



 


		13.3.	If
                                         the Parties cannot resolve the dispute or difference by referral to a senior representative
                                         of each Party, then within 15 days from the date of such meeting of the senior representatives,
                                         the matter shall be referred to a mediator to be agreed upon by Parties or, failing such
                                         agreement, shall be appointed on the application of either one of the Parties to the
                                         President of the Law Society of England and Wales. The Parties shall use reasonable efforts
                                         to resolve any dispute by mediation for a period of 60 days.



 


		13.4.	No
                                         waiver of any right under this Agreement shall be deemed effective unless contained in
                                         a written document signed by the Party charged with such waiver, and no waiver of any
                                         breach or failure to perform shall be deemed to be a waiver of any future breach or failure
                                         to perform or of any other right arising under this Agreement.



 


		13.5.	Neither
                                         Party to this Agreement shall be liable for delay or failure in the performance of any
                                         of its obligations hereunder to the extent such delay or failure results from causes
                                         beyond its reasonable control, including, without limitation, acts of God, fires, strikes,
                                         acts of war, or intervention of a government authority ("Force Majeure"),
                                         but any such delay or failure shall be remedied by such Party as soon as practicable.



 


		13.6.	JAVA
                                         shall not subcontract with a third party to perform the Services without the prior written
                                         consent of the Sponsor.



 


		13.7.	JAVA
                                         shall not be entitled to assign this Agreement to a third party, without the prior written
                                         consent of the Sponsor, which shall not be unreasonably withheld.



 


		13.8.	This
                                         Agreement shall be binding upon and inure to the benefit of the Parties hereto and their
                                         respective successors and permitted assigns.



 


		13.9.	Nothing
                                         contained in this Agreement is intended or is to be construed to constitute JAVA and
                                         the Sponsor as partners or members of a joint venture. None of the Parties hereto shall
                                         have any express or implied right or authority to assume or create any obligations on
                                         behalf of or in the name of the other Party or to bind the other Party to any contract,
                                         agreement or undertaking with any third party.



 




    	11



    	 



    

 


		13.10.	No
                                         amendment, modification or addition hereto shall be effective or binding on any Party
                                         unless set forth in writing and executed by a duly authorised representative of each
                                         of the Parties.



 


		13.11.	Any
                                         notice to be given under this Agreement shall be sent in writing in writing by recognized
                                         courier or registered mail to each of the Parties stated in this Agreement, in the Sponsor’s
                                         case to to Mr. Simcha Rock, Kitov Pharmaceuticals, Bet Hadfus 11 Jerusalem, or
                                         to such other address(es) as may from time to time be notified by any of the Parties,
                                         in the Sponsor’s case by the office of Corporate and Legal Affairs, to the others
                                         hereunder.



 


		13.12.	Any
                                         notice sent by overnight courier or registered mail shall be deemed to have been delivered
                                         upon receipt by the addressee.



 


		13.13.	If
                                         any provision in this Agreement is agreed by the Parties to be, or is deemed to be, or
                                         becomes invalid, illegal, void or unenforceable under any law that is applicable hereto:-



 


		13.13.1.	such
                                         provision will be deemed to be deleted, and the Parties shall promptly meet and negotiate
                                         in good faith a valid and enforceable replacement for the severed provision which replacement
                                         shall be designed to achieve as nearly as possible the same commercial objective as the
                                         original; and



 


		13.13.2.	the validity, legality and
enforceability of the remaining provisions of this Agreement shall not be impaired or affected in any way.



 


		13.14.	This
                                         Agreement sets forth all of the agreements and understandings between the Parties with
                                         respect to the subject matter hereof, and supersedes and terminates all prior agreements
                                         and understandings between the Parties with respect to the subject matter hereof.



 


		13.15.	At
                                         the request of any of the Parties, the other Party shall (and shall use reasonable efforts
                                         to procure that any other necessary third parties shall) execute and do all such documents,
                                         acts and things as may reasonably be required subsequent to the signing of this Agreement
                                         for assuring to or vesting in the requesting Party the full benefit of the terms hereof.



 


		13.16.	The
                                         provisions of Clauses 1, 6, 7, 9, 10, 11, 12, and 13 shall survive the termination of
                                         this Agreement or any Work Order.



 


		13.17.	This
                                         Agreement may be executed in any number of counterparts, each of which when so executed
                                         shall be deemed to be an original and all of which when taken together shall constitute
                                         this Agreement.



 




    	12



    	 



    

 


IN WITNESS
WHEREOF, the Parties hereto have executed this Agreement.


 


	SIGNED by	 /s/
    Simcha Rock 	 


Chief Financial
Officer


 


for and on
behalf of


KITOV PHARMACEUTICALS
LTD (“Kitov”)


 


DATE: February
9, 2014


 


	SIGNED by	 /s/
    Ruth Nullen 	 


(Managing Director)


 


for and on
behalf of


JAVA CLINICAL
RESEARCH LIMITED 


 


DATE: February
6, 2014


 




    	13



    	 



    

 


APPENDIX
1


WORK ORDER
NO 1


 


This WORK
ORDER dated as of the date of last signature below


 


BETWEEN


 


		(1)	Kitov
                                         Pharmaceuticals Limited (“Kitov”) Company incorporated in Israel whose
                                         registered address and principal place of business is at, 11 Bet Hadfus Street, Jerusalem,
                                         Israel.



("Sponsor");
and


 


		(2)	JAVA
                                         CLINICAL RESEARCH LIMITED, a company incorporated in Ireland, registered number 311398,
                                         with registered office address 2 Grand Canal Square, Dublin 2, whose principal place
                                         of business is at Fitzwilliam Business Centre, 26/27 Upper Pembroke Street, Dublin 2
                                         ("JAVA")



 


WHEREAS


 


		A.	The
                                         Sponsor and JAVA are bound by the terms of the Master Services Agreement dated 04 February
                                         2014 between the Sponsor and JAVA (the "Master Services Agreement").



 


The
Sponsor and JAVA wish to set out the specific details of services to be provided by JAVA in respect of A Prospective Randomized
Placebo Controlled Study to Evaluate the Effect of Celecoxib on the Efficacy  and Safety
of Amlodipine in Subjects with Hypertension Requiring Antihypertensive Therapy


 


(the
"Project").


 


THE PARTIES
NOW HEREBY AGREE AS FOLLOWS:


 


		1.	JAVA
                                         shall provide the services as outlined in Schedule 2 hereto (the "Services")
                                         in accordance with the timelines set out in Schedule 3 hereto and the terms and conditions
                                         of the Master Services Agreement together with the additional provisions as set out in
                                         the following Schedules:



 


Schedule 1
Scope of Services


Schedule 2
Timelines


Schedule 3
Budget and Payment Schedule


Schedule 4
Personnel / Contacts for Notices and Payments


Schedule 5
Protocol


 


		2.	This
                                         Work Order has an effective date as of the last date of signature and will remain valid
                                         until completion of Services described herein and when the Sponsor has paid the final
                                         invoice in accordance with the terms of the Master Services Agreement, unless otherwise
                                         terminated in accordance with the provisions of Clause 12 of the Master Services Agreement.



 




    	14



    	 



    

 


SIGNED
BY


 


KITOV PHARMACEUTICALS
LIMITED


 


Signature:  /s/
Simcha Rock     


 


By:       
Simcha Rock                     


(Print
Name)


Title:
          Chief Financial Officer      


 


Date:
         February 9, 2014       


 


JAVA
CLINICAL RESEARCH LIMITED


 


Signature:   /s/
Ruth Nullen       


 


By:        Ruth
Nullen     


(Print
Name)


Title:
Managing Directoe         


 


Date:
    February 6, 2014     


 




    	15



    	 



    

 


SCHEDULE
1: SCOPE OF SERVICES


 




    	16



    	 



    

 


Study
Title: A Prospective Randomized Placebo Controlled Study to Evaluate the Effect of Celecoxib
on the Efficacy and Safety of Amlodipine in Subjects with Hypertension Requiring Antihypertensive Therapy


 


PROTOCOL
NO.: K-302-03-01


 


Proposed
Allocation of Sponsor - Java- Duties and Functions


 


04
February 2014


 


		I.	Regulatory
                                         and Ethics



 


		II.	Investigator
                                         Relations



 


		III.	IMP
                                         Supplies



 


		IV.	Study
                                         Documentation



 


		V.	Relationship
                                         between Sponsor& Java



 


		VI.	Relationship
                                         with other subcontractors



 


		VII.	Monitor
                                         Activities of Clinical Sites



 


		VIII.	Medical
                                         and coherence review of the CRF following retrieval from the site



 


		IX.	Serious
                                         Adverse Events follow up and reporting



 


		X.	Data
                                         entry, Data Management & Coding



 


		XI.	Statistical
                                         Analysis



 


		XII.	Clinical
                                         Study Report



 


		XIII.	XIV
                                         Medical Monitoring



 


		XIV.	Quality
                                         Assurance 



 




    	17



    	 



    

 


table
of responsibilities: E = Execute; A = Assist; R = Review


 


*
= Subcontracted by Java to a third party Vendor


 


#
= Subcontracted by SPONSOR to a third party Vendor


 


	 	 	Sponsor	 	JAVA
	I              Regulatory
    & Ethics	 	 	 	 
	1.    Provision of all supporting IMP documentation for CTA  submission to IMB and MHRA.	 	E	 	R
	2.    Completion
    of EudraCT Form, compilation of supporting documents (on receipt from relevant parties) into required electronic format for
    submission of Clinical Trial Application to IMB and MHRA, plus submission of responses to any queries raised during review
    period	 	 	 	E
	3.    Submission
    of CTA to National Ethics Committees in Republic and Northern Ireland plus submission of responses to any queries raised during
    review period	 	 	 	E
	4.    Providing
    Sponsor with the final answer given by IMB. MHRA and Ethics Committees	 	 	 	E
	II          Investigator
    Relations	 	 	 	 
	A.
     Selection	 	 	 	 
	1.    Definition
    of investigator selection criteria	 	E	 	 
	2.    Proposal
    of potential investigators and national coordinator	 	 	 	E
	3.    Organization
    of site assessment visits to evaluate the interest and suitability of the centers to participate in the study.	 	 	 	E
	4.    Approval
    of selected investigators	 	A	 	E
	5.    Organization
    of pre-trial visits with all investigators to evaluate the capability of the centers to recruit patients within the time frame,
    advise them of the study requirement and procedures in preparation for Site Initiation	 	 	 	E


 




    	18



    	 



    

 


	 	 	Sponsor	 	JAVA
	B
    Investigator fees	 	 	 	 
	1.    Proposal
    of investigator fees and payment schedule for each involved country	 	A	 	E
	2.    Proposal
    and negotiation of the fees to the investigators	 	 	 	E
	3.    Approval
    of final investigator fees	 	E	 	 
	4.    Management
    of payment of investigator fees and issue of invoices to Sponsor	 	 	 	E
	C.
    Agreement with investigators/institutions	 	 	 	 
	1.    Issue
    of Confidentiality Agreements to be signed by investigators	 	 	 	E
	2.    Identification
    of all the agreements to be obtained before study start	 	A	 	E
	3.    Drawing
    up of all agreements	 	A	 	E
	4.    Submission
    of the agreements to the investigators/institutions for approval and signature	 	 	 	E
	5.    Signature
    of the agreements	 	E	 	A
	6.    Collection
    of specific FDA  documentation  requirements such as 1572 forms as requested by Sponsor	 	R 	 	E
	III        IMP
    Supplies	 	 	 	 
	 	 	 	 	 
	A.
Randomization/allocation of treatments	 	 	 	 
	1.    Programming,
    development of a randomisation list	 	E#	 	 
	2.    Issue
    of decoding envelopes to be sent to investigators for decoding in case of medical emergency	 	E#	 	 
	3.    Allocation
    of treatments through a Central Randomisation system	 	E#	 	 
	4.    Shipment
    of initial  treatment blocks  of IMP to site	 	E#	 	 
	5.    Approval
     of additional reorders form sitesite 	 	R	 	E
	6.    Shipment
    of additional reorders to site	 	E#	 	 


 




    	19



    	 



    

 


	 	 	Sponsor	 	JAVA
	B.
    Management of trial drug supplies	 	 	 	 
	1.    Manufacturing
    of drug supplies (or subcontracting)	 	 E#	 	 
	2.    Management
    of subcontracting for packaging, labeling and shipment to sites	 	 E#	 	 
	3.    Validation
    of labeling regarding administrative and regulatory procedure in each involved country	 	 	 	E
	4.    Submission
    of import license when applicable	 	E#	 	 
	5.    Management
    of all customs issues	 	E#	 	 
	6.    Forwarding
    of required regulatory documentation to Sponsor for allowing the shipment of clinical supplies to each site	 	 	 	E
	C.
    Retrieval and disposal of study drug	 	 	 	 
	1.    Manage
    retrieval of study drug from each site	 	E#	 	E
	2.    Manage
    destruction of study drug.	 	E#	 	 
	3.    Perform
    a reconciliation of all drugs supplied and returned to Sponsor	 	E#	 	E
	IV       Study
    documentation	 	 	 	 
	A.
Drawing up study documents	 	 	 	 
	1.    Final
    protocol	 	E	 	 
	2.    Patient
    Information Leaflet and Informed Consent Form development 	 	R	 	E
	3.    Approval
    of Patient Information Leaflet and Informed Consent Form	 	E	 	 
	4.    eCRF
    development	 	R	 	E*
	5.    Approval
    of eCRF	 	E	 	 
	6.    Printing
    of CRFs, if applicable	 	N/A	 	N/A
	7.    Monitoring
    Guidelines and their update	 	R	 	E
	8.    Approval
    of Monitoring Guidelines	 	E	 	 
	9.    Laboratory
    Operating Manual development	 	 	 	E*
	10. 
    Approval of Laboratory Operating Manual	 	E	 	 
	11. 
    ABPM Manuals development and approval	 	E#	 	R



 






    	20



    	 



    

 


	 	 	Sponsor	 	JAVA
	B.
Filing and archiving of study document	 	 	 	 
	1.    Preparation
    of the Investigator’s Trial Files 	 	 	 	E
	2.    Filing
    of all original administrative study documents according to mutually agreed SOP (Trial Master File)	 	 	 	E
	3.    Provide
    Sponsor on an ongoing basis with:	 	 	 	 
	-
    CRO personnel CVs and Allocation of duties and functions form	 	 	 	E
	-
    Regulatory filing of declaration and any correspondence or contact with Regulatory Authorities	 	 	 	E
	-
    Approval letters or acknowledgement letters of Regulatory Authorities	 	 	 	E
	-
    Approval letters and any correspondence with Ethics committees	 	 	 	E
	-
    Protocol signature page signed by Sponsor and the investigators	 	 	 	E
	-
    Trial and Financial Agreements with Sponsor signed by the investigators	 	 	 	E
	- CVs from site personnel
    and Trial Site Signature forms	 	 	 	E
	-1572
    form and any other FDA documents required by the Sponsor	 	 	 	E
	4.    Ensure
    that patients' names and addresses are masked prior to returning documents to Sponsor but assure that the documents are still
    identifiable with protocol number, patient's initials and number	 	 	 	E
	5.    Assure
    the maintenance and archiving at the trial sites of the Investigators’ Trial Files and CRFs	 	 	 	E
	6.    Provide
    all original documents of the Trial Master File upon request of Sponsor, after database closure	 	 	 	E
	V         Relationship
    between Sponsor and Java 	 	 	 	 
	A.
CRO clinical team	 	 	 	 
	1.    Assignment
    of a clinical team dedicated to the study	 	 	 	E
	2.    Regular
    contacts (teleconference), , between Java and Sponsor representatives; initially weekly  then frequency will depend
    on the ongoing issues to be discussed	 	A	 	E


 




    	21



    	 



    

 


	 	 	Sponsor	 	JAVA
	B. Reporting	 	 	 	 
	1.    Preparation
    and forwarding every week to Sponsor of a study report concerning the status of patients per site : number of patients included,
    dropped out, randomised, treatment ongoing, completed, recruitment rate (% included/to be included)	 	 	 	E
	2.    Preparation
    and forwarding every two months to Sponsor of a report concerning the activities in terms of patient visits to allow payments
    of fees	 	 	 	E
	3.    
    Monthly report of monitoring activities: type and date of visit, report date, problems, actions taken	 	 	 	E
	4.    
    CRF tracking per centre: CRF visits monitored, laboratory results monitored, deviations to protocol, quality of the data,
    number of SAEs will be included in each monitoring report.	 	 	 	E
	VI
        Relationship with the Central Laboratory

        Negotiation
        and signature of agreement with central laboratory 
	 	 	 	E*
	A.   Proposal
    of a central laboratory for 	 	 	 	 
	1.    Biochemistry
    & Haematology Profile	 	 	 	 
	2.    Urine
    Drug Screen	 	 	 	 
	3.    Urinalysis
    & Pregnancy	 	 	 	E*
	4.    Alcohol
    Detection	 	 	 	 
	 	 	 	 	 
	        B.       Preparation
    of 	 	 	 	 
	1.    Investigator
    Laboratory Manual	 	 	 	 
	2.    Multi
    Part Laboratory Reports	 	 	 	E*
	Tailor made request forms
    & patient labelling	 	 	 	 


 


	  C. Collection of specimens 	 	 	 	E*
	1.   Logistics
    and transportation in accordance with ADR regulations under temperature controlled conditions (ambient, +4°C or -20°C).
    	 	 	 	 
	2.   Analysis
    of specimens as required during normal working hours. 	 	 	 	 


 




    	22



    	 



    

 


	 	 	Sponsor	 	JAVA
	   D. Reporting Procedures	 	 	 	
	1.    Authorized
    report on the results from each patient specimen. 	 	 	 	 
	2.    Expert
    medical pathologist support where result interpretation and clinical advice is required. 	 	 	 	E* 
	3.    Post Analysis Storage of Sampl	 	 	 	 
	 	 	 	 	 
	E. Disposing of samples	 	 	 	 
	1.    OpenLabs
    Web Browser enabling Secure 	 	 	 	 
	Access to Patient Results
    over the Internet 	 	 	 	 
	2.    Full
    Extraction of results for all sample post analysis as per client request. 	 	 	 	E*
	3.    Resolution
    of queries in a timely manner,queries relating to sample requests	 	 	 	 
	1.	 	 	 	 
	VII – Monitor activities
    on clinical sites	 	 	 	 
	A.
    Pre-Initiation and Site Initiation Visits	 	 	 	 
	1.    Performing
    site assessment visits	 	 	 	E
	2.    Performing
    pre-study visits	 	 	 	E
	3.    Performing
    all the site initiation visits as soon as possible after obtaining all required regulatory documents	 	 	 	E
	4.    Assure
    that all critical points of the study including scientific, administrative and logistic matters are well understood by all
    members of the study team prior to enrollment of the first patient at a site	 	 	 	E
	5.    Check
    that all study documents and/or material such as eCRF manual, investigator study file, investigator operating manual have
    been forwarded to the investigator prior to the Site Initiation Visit or handed over during the visit	 	 	 	E
	6.    Retrieval
    of any outstanding essential study documents to be signed by the investigator at the latest (if not, study drugs cannot be
    released and the investigator is not allowed to include patients)	 	 	 	E


 




    	23



    	 



    

 


	 	 	Sponsor	 	JAVA
	7.    Management
    of all regulatory and logistical matters with the study pharmacist, if applicable	 	 	 	E
	B. 
    Patient selection and recruitment	 	 	 	 
	1.    Monitor
    patient recruitment at the sites in order to ensure the target number of patients, as defined in the protocol and in accordance
    with the the planned study timelines, is met	 	 	 	E
	2.    Decision
    to increase the number of sites, if needed	 	E	 	 
	C.
  Monitoring	 	 	 	 
	1.    Allocation
    of internal experienced CRAs to monitor the study	 	 	 	E
	2.    Performing
    all monitoring activities related to the study, including investigators’ site monitoring according to Monitoring Guidelines
    and agreed SOPs. The rate of monitoring visits will be defined in the Monitoring Plan.	 	 	 	E
	3.    Monitoring
    of pharmacy  where applicable 	 	 	 	E
	4.    Detection
    and report to Sponsor potential problems as well as possible proposed actions to be discussed with the Sponsor	 	 	 	E
	5.    Verification
    of source documents for 100% of randomised patients for the key-criteria (inclusion/exclusion criteria, primary endpoint assessments,
    AEs (serious and non-serious), drug dispensing record and informed consent forms, reason for premature termination)	 	 	 	E
	6.    
    The monitor will ensure site personnel address all corrections/ discrepancies on the eCRF pages during, or following each
    monitoring visit.  The monitor will also ensure site addresses data queries when generated by CROSNT, as per CROSNT’s
    query handling procedure 	 	 	 	E
	7.    Review
    of biological results filing and  their masking 	 	 	 	E
	8.    Check
    of maintenance and update of the investigatorss trial files at routine monitoring visits	 	 	 	E


 




    	24



    	 



    

 


	 	 	Sponsor	 	JAVA
	9.    Completion
    of a visit report form and forwarding to Sponsor within 10 working days after each visit (site assessment, pre-study, site
    initiation, monitoring, close-out)	 	 	 	E
	10.  Co-monitoring
    visits with the CRO at investigator’s site according to a mutually agreed rhythm described in the Monitoring Plan	 	E	 	 
	D.
    Drug accountability	 	 	 	 
	1.    Check
    of 100% study drug accountability and storage conditions	 	 	 	E
	2.    Check
    that the product is dispensed in conformity with the centralized allocation procedure 	 	 	 	E
	3.    Check
    that Drug Dispensing and Accountability Forms are complete and accurate	 	 	 	E
	E. Study closure	 	 	 	 
	1.    Perform
    close-out visit to the sites on Sponsor’s instruction	 	 	 	E
	2.    Check
    that essential documents are archived properly on site	 	 	 	E
	3.    Collect
    all unused study materials	 	 	 	E
	VIII       Medical
    and coherence review of the eCRF following retrieval from the site	 	 	 	 
	1.    Medical
    review in order to ensure validity and consistency of the information contained within the CRFs, specifically: past medical
    history, inclusion/exclusion criteria, concomitant illnesses, forbidden treatments, clinical examination and vital signs,
    follow-up of adverse events, follow-up of serious adverse events (hospital report...), ancillary examinations.	 	E	 	 
	IX         Serious
    Adverse Events follow up and reporting	 	 	 	 
	1.    Provide
    investigator sites with SAE forms	 	R	 	E*
	2.    Monitoring
    and collection of Serious Adverse Events follow-up and additional documentation such as discharge reports	 	 	 	E
	3.    Eudravigilance
    registration	 	 	 	E*
	4.    Responsible
    Person for Eudravigilance	 	 	 	E*
	5.    Safety
    Database	 	 	 	E*


 




    	25



    	 



    

 


	 	 	Sponsor	 	JAVA
	6.    Review
    of all Serious Adverse Events forms on an ongoing basis	 	 	 	E*
	7.    Shipment
    of SUSARs reports and annual safety reports to Competent Authorities	 	 	 	E*
	8.    Shipment
    of Development Safety Update Reports to Competent Authorities	 	E	 	 
	9.    Shipment
    of SUSARs reports and annual safety reports to Ethics Committees (reports provided by Sponsor)	 	 	 	E
	X     Data-Entry, Data
    management and Coding	 	 	 	 
	A.
    eCRF completion 	 	 	 	 
	1.    The
    monitor will check that all monitored data eCRF are entered in the eCRF database. The monitor will ensure that the Principal
    Investigator signs the eCRF signatory page at the end of the study once all data queries have been addressed	 	 	 	E
	B. Data management
    	 	 	 	 
	1.    CRF
    Design	 	R	 	E*
	2.    Data
    Management Plan	 	R	 	E*
	3.    Programming
    and Validation of Database	 	R	 	E*
	4.    Programming
    and Validation of Consistency Checks	 	R	 	E*
	5.    Data
    Load set-up	 	 	 	E*
	6.    User
    acceptance testing	 	R	 	E*
	7.    CRF/DCF
    Tracking and Archiving	 	 	 	E*
	8.    Lab
    imports	 	 	 	E*
	9.    Data
    Entry	 	 	 	E*
	10.  Data
    Cleaning	 	 	 	E*
	11.  SAE
    Reconciliation	 	 	 	E*
	12.  Production
    of Listing for Medical Review	 	R	 	E*
	13.  Coding	 	 	 	E*
	14.   Metrics/Tracking
    Report	 	 	 	E*
	15.   Documentation
    Archiving	 	 	 	E*
	16.   Database
    Lock	 	 	 	E*
	17.   Database
    Transfer	 	 	 	E*
	XI   Statistical
    analysis	 	 	 	 
	1.    Responsibility
    for statistical analysis other than ABPM	 	R	 	E*


 




    	26



    	 



    

 


	 	 	Sponsor	 	JAVA
	2.    Responsibility
    for statistical analysis of ABPM	 	E	 	 
	XII    Clinical study
    report	 	 	 	 
	            Clinical
    Study Report (excluding ABPM) 	 	R	 	E*
	XIII Medical Monitoring
    	 	 	 	 
	 Primary contact
    for all medical queries	 	E	 	 
	XIV    Quality
    Assurance	 	 	 	 
	1    Issue
    of audit plans for the trial.	 	E	 	 
	2    Conduct
    on site QA audits	 	E	 	 
	3    Implement
    corrective actions and follow up with sites	 	 	 	E


 


SCHEDULE
2-: TIMELINES


 


The Work Order
is based on the following proposed timelines and is is dependent that all supporting documentation for CTA submissions to The
IMB and MHRA are available week commencing 24th February.


 


	Project Preparation	January- April 2014
	EC & CTA Approvals 	May 2014
	First Site Initiation Visit	May 2014
	First Patient First Visit	June 2014
	Last Patient Last Visit	October 2014
	 Data Base Lock 	 TBC ( based on results of interim analysis)  


 




    	27



    	 



    

 


SCHEDULE
3: BUDGET AND PAYMENT SCHEDULE


 




    	28



    	 



    

 


	Study
    Reference K-03-01	 
	 	 
	Projected
    Timelines:	 
	Project Preparation	14 weeks
	Study Recruitment
    and Conduct Period	22 weeks
	Close out period	12 weeks 
	 	 
	Indication:	Hypertension 
	 	 
	Key
    Assumptions:	 
	Number of patients
    to be screened	300
	Number of patients
    to be randomised	150
	Sites	10 sites Republic/Northern
    Ireland
	Number of monitoring
    visits	Estimated pool
    of 60 monitoring site visits
	Total
    CRF pages per patient	TBC
	 	 


 


		 	RATE	 	 		 	EST. REQ.	 	ESTIMATED 

CHARGE	 	 	
	ACTIVITY 	 	€	 	 	UNIT	 	Range	 	Range
    €	 	 	Comments 
	Project Preparation	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	PM project training	 	 	110.00	 	 	hour	 	16	 	 	1,760.00	 	 	To include protocol, CRF and SOP training
	CRA project training	 	 	85.00	 	 	hour	 	16	 	 	1,360.00	 	 	To include protocol, CRF and SOP training
	PM project preparation time	 	 	1,760.00	 	 	week	 	14	 	 	24,640.00	 	 	Includes site contacts/feasibility assessments to
    ensure all required systems are in place for study initiation, assistance with eCRF development to include advice on required
    CRF data fields, communication with Kitov Ltd on project related progress/issue
	CRA project preparation time	 	 	1,360.00	 	 	week	 	14	 	 	19,040.00	 	 	Includes site contacts/feasibility, communication
    with Kitov Ltd, collating all study related materials required for initiation, addressing site queries and issues, preparation/customisation
    of Investigator Study Files and Forms, collection of essential d
	CTA project preparation time	 	 	400.00	 	 	week	 	14	 	 	5,600.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Preparation
    total	 	 	 	 	 	 	 	 	 	 	52,400.00	 	 	 
	Regulatory and Ethics	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Review and submission of CTA to IMB (including submission
    of responses to any queries raised during review period)	 	 	3,840.00	 	 	submission	 	1	 	 	3,840.00	 	 	 
	Review and submission of CTA to MHRA (including submission
    of responses to any queries raised during review period)	 	 	3,840.00	 	 	submission	 	1	 	 	3,840.00	 	 	 
	Submission to National Ethics Committee in Repbulic
    of Ireland (including submission of responses to any queries raised during review period)	 	 	2,040.00	 	 	submission	 	1	 	 	2,040.00	 	 	 
	Submission to National Ethics Committee in Northern
    Ireland (including submission of responses to any queries	 	 	2,720.00	 	 	submission	 	1	 	 	2,720.00	 	 	 
	Management of Site Specific Approvals for all sites	 	 	340.00	 	 	site	 	10	 	 	3,400.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Regulatory
    total	 	 	 	 	 	 	 	 	 	 	15,840.00	 	 	 
	Clinical Operations	 	 	 	 	 	 	 	 	 	 	 	 	 	Assuming 4 Dublin Centres: 6 Regional Centres -  estimated
    Monitoring Visit Pool of 60 site visits
	Site Qualification Visits	 	 	680.00	 	 	site	 	10	 	 	6,800.00	 	 	 
	Travel time	 	 	400.00	 	 	site	 	6	 	 	2,400.00	 	 	Site Visit preparation time for pre study visits and
    monitoring
	Pre-Study Visits	 	 	850.00	 	 	site	 	10	 	 	8,500.00	 	 	visits - 2 hours. Site Visit preparation time for
    SIV and
	Travel time	 	 	400.00	 	 	site	 	6	 	 	2,400.00	 	 	close out visit - 4 hours.  Site Qualification
    and Pre study visit duration - 4 hours.
	Site Initiation Visits	 	 	1,360.00	 	 	site	 	10	 	 	13,600.00	 	 	SIV, monitoring and close out visit duration -
	Travel time	 	 	400.00	 	 	site	 	6	 	 	2,400.00	 	 	 
	Study Monitoring Visits	 	 	1,190.00	 	 	site	 	60	 	 	71,400.00	 	 	 
	Travel time	 	 	400.00	 	 	site	 	6	 	 	2,400.00	 	 	 
	Study Close-Out Visits	 	 	1,360.00	 	 	site	 	10	 	 	13,600.00	 	 	 
	CRA Site Management	 	 	1,020.00	 	 	week	 	34	 	 	34,680.00	 	 	Communication/liaison with Project Manager and site
    personnel on study related issues, progress etc; eCRF review (only as preparation for the monitoring visit); participation
    in project teleconferences, when required.
	Project Management	 	 	2,200.00	 	 	week	 	34	 	 	74,800.00	 	 	Internal management of CRAs including advice on recruitment
    strategies, site related issues, contingency measurement implementation etc; Communication with Kitov Ltd on project progress/study
    related issues; Management of Third Party Vendors; Management o
	CTA study conduct	 	 	400.00	 	 	week	 	34	 	 	13,600.00	 	 	Assistance with compilation of return of essential
    dcoument for TMF, CRA travel arrangements, collation of all pass through costs and study related invoices.
	Clinical Operations	 	 	 	 	 	 	 	 	 	 	246,580.00	 	 	 
	Other Services	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Clinical Laboratory Services (Estimate)	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Sample Analysis	 	 	 	 	 	 	 	 	 	 	37,020.00	 	 	 
	Central Laboratory Fee	 	 	 	 	 	 	 	 	 	 	2,700.00	 	 	 
	Web Browser Access	 	 	 	 	 	 	 	 	 	 	FOC	 	 	 
	Results Extraction	 	 	 	 	 	 	 	 	 	 	300.00	 	 	 
	Sample Collection Logistics Estimate	 	 	 	 	 	 	 	 	 	 	5,000.00	 	 	 
	Clinical Laboratory Services Subtotal	 	 	 	 	 	 	 	 	 	 	45,020.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Data Management and Statistics	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Biometrics Management	 	 	 	 	 	 	 	 	 	 	11,172.00	 	 	 
	Data Management	 	 	 	 	 	 	 	 	 	 	42,873.50	 	 	 
	eCRF management and hosting	 	 	 	 	 	 	 	 	 	 	64,189.25	 	 	 
	Statistics	 	 	 	 	 	 	 	 	 	 	37,225.75	 	 	 
	Data Management and Statistics
    Subtotal	 	 	 	 	 	 	 	 	 	 	155,460.50	 	 	 
	Pharmacovigilance	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Safety Database Maintenance	 	 	 	 	 	 	 	 	 	 	4,000.00	 	 	 
	PhV Specifications	 	 	 	 	 	 	 	 	 	 	2,910.00	 	 	 
	SAE Initial/Follow-up Report Processing	 	 	 	 	 	 	 	 	 	 	3,600.00	 	 	 
	Expedite SUSARs reporting	 	 	 	 	 	 	 	 	 	 	108.00	 	 	 
	Line Listing production	 	 	 	 	 	 	 	 	 	 	2,440.00	 	 	 
	Responsible Person - Eudravigilance	 	 	 	 	 	 	 	 	 	 	6712.5	 	 	 
	Pharmacovigilance Subtotal	 	 	 	 	 	 	 	 	 	 	19,770.50	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Medical Writing	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Clinical Study Report	 	 	 	 	 	 	 	 	 	 	14,252.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Other Services
    Subtotal	 	 	 	 	 	 	 	 	 	 	234,503.00	 	 	 
	8% Overhead	 	 	 	 	 	 	 	 	 	 	18,760.24	 	 	 
	SUBTOTALS	 	 	 	 	 	 	 	 	 	 	253,263.24	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	GRAND TOTAL  PROFESSIONAL
    FEES	 	 	 	 	 	 	 	 	 	 	568,083.24	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Other study conduct  costs	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	IMB CTA	 	 	 	 	 	 	 	 	 	 	1,443.00	 	 	 
	MHRA CTA	 	 	 	 	 	 	 	 	 	 	3,982.00	 	 	 
	Ethics Committe Fees	 	 	 	 	 	 	 	 	 	 	2,350.00	 	 	 
	CRA Travel	 	 	 	 	 	 	 	 	 	 	23,400.00	 	 	Dublin sites 4 sites x 10 visits x €30 per visit
    = €1200
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	Regional sites: 6 sites x 2 visits x €250 = €3000
    (SQV/PS)
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	Regional sites: 6 sites x 8 visits x €400 = €19,200
	Courier Costs - as per receipted expenses	 	 	 	 	 	 	 	 	 	 	5,000.00	 	 	Estimate
	Stationary, Printing, Photocopying for TMF, Investigator
    Site Files and Ethics Applications	 	 	 	 	 	 	 	 	 	 	10,000.00	 	 	 
	Management of PI fees	 	 	 	 	 	 	 	 	 	 	9,885.00	 	 	 
	Estimate other pass through costs	 	 	 	 	 	 		 	 	 	56,060.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Proposed payment schedule	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	15% upfront fee at exchange of contracts	 	 	 	 	 	 	 	 	 	 	85,212.49	 	 	 
	15% first Competent Authority approval (IMB or MHRA)	 	 	 	 	 	 	 	 	 	 	85,212.49	 	 	 
	10% following 30 subjects randomised	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% following 60 subjects randomised	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% following 90 subjects randomised	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% following 120 subjects randomised	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% following 150 subjects randomised	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% DB lock	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	10% final study report	 	 	 	 	 	 	 	 	 	 	56,808.32	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	568,083.24	 	 	 
	Pass through fees	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	20 % upfront  fee at exchange of contracts	 	 	 	 	 	 	 	 	 	 	11,212.00	 	 	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Monthly based on actual expenses incurred.	 	 	 	 	 	 	 	 	 	 	 	 	 	 



 




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SCHEDULE
4 -: PERSONNEL/CONTACTS FOR NOTICES


Sponsor
Personnel


 


	Country	 	Name 	 	Role 	 	Phone	 	Email address
	Israel	  	Simcha Rock	  	CFO	  	+972

        625

        4142
	  	simcha@kitovpharma.com


 


Java
Personnel


 


	Country	 	Name 	 	Role 	 	 Phone 	 	Email address
	Ireland	  	Ruth Nallen	  	Managing Director	  	+353 1 

    6373903	  	rnallen@javacr.com


 




    	30



    	 



    

 


SCHEDULE
5 -: PROTOCOL


 




    	31