EX-10.13



 Exhibit 10.13 
  





 
 SERVICE AGREEMENT 

FOR A CLINICAL STUDY CONDUCT 
 concluded on
16 December 2013 (“Effective Date”) in Warsaw by and between: 
 KCR S.A. (Polish joint-stock company) with its registered office in
Warsaw at 6 Postępu Str., 02-676 Warsaw, Poland, entered in the register of entrepreneurs kept by the District Court for the Capital City of Warsaw in Warsaw, 13th Commercial Division of the National Court Register, under number 0000289542, tax
identification number NIP: 521-31-69-665, share capital (covered in total): PLN 700,000.00, hereinafter referred to as “CRO”, represented by Mr. Mike Jagielski – President of the Management Board and Ms. Anna Baran
– Vice President of the Management Board, 
 and 

Vascular Biogenics Ltd., its principal place of business at 6 Jonathan Netanyahu Street, Or Yehuda, Israel 60376 hereinafter referred to as
“Sponsor”, represented by Prof. Dror Harats—Chief Executive Officer, 
 hereinafter jointly referred to as „the Parties” and
individually as a “Party”. 
 Whereas: 
  

	 	a)	Sponsor intends to conduct a clinical study of the investigational medicinal product VB-201 [„Investigational Medicinal Product”] entitled “A Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled
Study to Evaluate the Efficacy and Safety of Oral VB-201 in Patients with Moderate to Severe Plaque Psoriasis” [„Study”] according to the protocol number VB-201-079 [“Protocol”] on the territory of Poland, 


 

	 	b)	Legal Representative of the Sponsor is SCIderm GmbH, a company organized and existing under the laws of Federal Republic of Germany, entered in the Trade Register maintained by the District Court in Hamburg, under the
number HRB 93824 with its registered office at Drehbahn 1-3, 20354 Hamburg, Germany, 

  

	 	c)	Sponsor wishes to engage CRO to provide services connected with the conduct of the Study as defined herein, 

  

			
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	 	d)	fulfillment of CRO’s obligations resulting from this agreement is included in the scope of CRO’s business activity and CRO has an experience in providing services of similar nature as described herein,
including the fact that CRO employs qualified employees in order to perform such obligations. 

 Now then, the Parties agree to
conclude the agreement as follows [„Agreement”]: 
 § 1. Subject of the Agreement 

 

	1.	Sponsor hereby entrusts CRO with performance of activities connected with the conduct of the Study as defined in Attachment No. 1 hereto (Scope of Services), hereinafter referred to as „Services”, and CRO
hereby accepts such entrusted responsibilities. 

  

	2.	Services shall be performed within the timelines indicated in Attachment No. 2. Parties declare that these timelines shall be deemed as a forecast only and may be changed due to reasons which are not attributable
to the CRO. In case of necessity to provide Services within different timelines than those anticipated in Attachment No. 2 for reasons not attributable to CRO, Sponsor waives its right to bring any claims against CRO for an untimely provision
of Services. 

 § 2. Manner of Providing Services 

 

	1.	CRO shall perform its responsibilities, in the scope indicated in the Agreement, with due diligence and in compliance with laws and regulations in force applicable in the countries where the Services will be performed,
guidelines of Good Manufacturing Practice, Good Laboratory Practice, Good Clinical Practice, ICH GCP in a version applicable during the term of the Study conduct, in compliance with the Agreement and a valid version of the Protocol, constituting
Attachment No. 3 to the Agreement, CRO’s SOPs listed in Attachment No. 4 and any written instructions of the Sponsor. 

  

	2.	 The CRO represents and warrants that it has obtained, and will maintain throughout the term of this Agreement, all governmental or regulatory
approvals, licenses, registrations and insurances that may be required to complete the Study, and that it has full right, power and authority to perform its obligations hereunder and to grant the rights set forth herein. During the term of this
Agreement the CRO shall not conduct any other trial which, at the CRO’s 



  

			
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discretion, would adversely affect the ability of the CRO to perform their obligations under this Agreement. 


 

	3.	In order to perform Services, CRO undertakes an obligation to appoint from among its employees only persons with appropriate knowledge, experience and qualifications necessary to perform Services, and who have bound by
confidentiality undertakings according to this Agreement. 

  

	4.	The CRO certifies that it has not and will not use in any capacity in connection with this Agreement the services of any individual, corporation, partnership, or association which has been debarred, excluded, or
disqualified from participation in clinical investigations under any applicable laws, regulations, or guidance. In the event that the CRO receives notice of the debarment or threatened debarment, exclusion or disqualification or threatened
disqualification, of any individual, corporation, partnership or association providing services to the CRO, which relate to its activities under this Agreement, the CRO shall notify the Sponsor immediately. 


 

	5.	If the Sponsor raises any objections regarding provision of Services by a particular CRO employee, the Sponsor shall notify CRO of that fact in writing and may request replacement of such employee solely due to material
and reasonable objections against his/her work or behavior. CRO shall appoint a new employee with appropriate qualifications and experience in the shortest possible time. 


 

	6.	Sponsor shall have the right to reject any Services that it deems in nonconformance with the Protocol or the Agreement. Sponsor shall provide CRO with written notification of the deficiency or non-conformance and,
within thirty (30) days of receipt of such written notification, CRO shall correct the deficiency or non-conformance at CRO’s expense. 

  

	7.	During the term of the Agreement and subject to the prior approval of the Sponsor (e-mail form is acceptable), CRO may entrust a third party, such as sites, investigators, and other relevant sub-contractors
(“Sub-contractors”) with performance of all or some of the Services while observing due diligence in this choice, provided that such Sub-contractors are made aware of and acknowledge the obligations applicable to such Sub-contractors
according to this Agreement including without limitation confidentiality, Intellectual property rights and publications. The CRO shall ensure, and shall at all times remain jointly and severally responsible and liable, for the compliance of such
Sub-contractors with the terms of this Agreement. For the avoidance of doubt, the Parties agree that this section shall not release 


  

			
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the Sponsor or the investigators from liability for the Study conduct according to provisions of law in force. 


 

	8.	CRO acknowledge that the Sponsor may entrust third parties with performance of services, which are related to the Study but are not included in the Services, which shall be provided by the CRO. A list of such third
parties attached hereto as Attachment 5 or as shall be amended by the Sponsor from time to time. CRO warrants that (i) it will fully cooperate with such third parties according to the Sponsor’s written instructions as necessary to the
conduct of the Study and (ii) it will be obligated by the relevant written instructions imposed by such third parties as shall be presented to the CRO by such third party or the Sponsor. 


 

	9.	CRO warrants that the assumptions underlying each Attachment and/or timeline have been arrived at in good faith by CRO, based upon its experience and professional judgment. In the event the CRO or Sponsor requests to
amend the Services, timelines or budget for a Study, the Parties agree to negotiate in good faith a written change order signed by the duly authorized representatives of the Parties. 


 

	10.	Both Sponsor and CRO shall carry, at its sole expense, with financially sound and reputable insurers, an insurance coverage with respect to the conduct of its business. 


§ 3. Sponsor’s responsibilities 

Sponsor undertakes an obligation in particular to: 
  

	 	a)	provide CRO with all information in its possession about the Investigational Medicinal Product necessary for the conduct of the Study, 


 

	 	b)	keep CRO informed on an ongoing basis about any new findings concerning safety of the Investigational Medicinal Product, 

  

	 	c)	supply CRO with the Investigational Medicinal Product manufactured in compliance with Good Manufacturing Practice, adequately packed and labeled, 


 

	 	d)	supply CRO with documentation necessary for conduct of the Study, including the valid version of the Protocol, Investigator’s Brochure and the Case Report Forms (CRF), 


 

	 	e)	conclude insurance agreement on third party liability of the Sponsor and investigators for damages related to the conduct of the Study, in compliance with laws in force and provide CRO with a valid copy of the insurance
policy confirming conclusion of such agreement, 

  

	 	f)	notify CRO immediately of any suspension of the Study or withdrawal of the approval for the conduct of the Study, 


  

			
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	 	g)	perform other responsibilities not assigned to the CRO and necessary for the conduct of the Study. 


§ 4. Audits and inspections 
  

	1.	On Sponsor’s reasonable request, CRO shall, at any time, provide the Sponsor with information on the status of the Services performed. In particular, the Sponsor may request CRO to prepare an activity report on the
Services performed by CRO. 

  

	2.	During the term of the Agreement, CRO undertakes an obligation to allow the Sponsor and any competent authorities and national, foreign and international bodies or organizations responsible for registration of medicinal
products and supervision, audit or inspection of clinical studies to conduct an audit, control or inspection of the Study as well as to access the records related to the Study conduct, and to monitor and audit the activities of the
investigators and members of the study teams during the Study (including inspection and audit of the facilities and procedures used in the Study by the investigators and the study teams, as well as the equipment, data registration method and storing
the records), and to enable both Sponsor and any national, foreign and international bodies or organizations responsible for registration of medicinal products and supervision or inspection of clinical studies to obtain any and all information on
the conduct of the Study. 

  

	3.	CRO shall notify Sponsor if any competent authorities and national, foreign and international bodies or organizations responsible for registration of medicinal products and supervision, audit or inspection of clinical
studies inform CRO about any scheduled, or begin an unscheduled inspection of any study site, CRO or bioethics committee. CRO shall immediately provide the Sponsor with any correspondence and/or communication related to a notification, conduct and
results of an audit or inspection and shall inform the Sponsor of the measures to be taken following finding and recommendations of such inspection and audits and their results. 


 

	4.	Sponsor agrees to cover the costs of CRO’s employees involvement in an audit, control or inspection based on real time spent on such activities according to the rates described in Attachment No. 6.



  

			
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 § 5. Remuneration 

 

	1.	For execution of all obligations resulting from the Agreement by CRO, Sponsor undertakes an obligation to pay remuneration as well as reimburse costs and expenses as defined in net amounts in Attachment No. 6. Due
VAT shall be added to the above fee. 

  

	2.	The Sponsor is obliged to make payments within 30 days from the receipt of a VAT invoice from CRO and provided that the CRO has provided upon the execution of this Agreement a Certificate of Residency from its Tax
Authorities. If it is necessary to convert one currency into another, it shall be calculated by CRO on the basis of a current foreign exchange selling rate of the Polish National Bank announced on the date of the VAT invoice issuance.


  

	3.	The remuneration shall be calculated and paid on a monthly basis for the time committed to or a type of Services provided in a given month within 30 days from the delivery of the invoice issued by CRO to the Sponsor.
CRO shall be entitled to issue and deliver a VAT invoice beginning with the last day of a given month for the amount covering time or type of Services performed in such month. 


 

	4.	On Sponsor’s request, CRO shall submit a list of Services performed in a given month, including a timesheet of persons providing Services with a detailed description of activities performed. 


 

	5.	The Sponsor shall reimburse CRO: 

  

	 	a)	for any costs incurred by CRO in connection with conclusion of the Agreement and providing the Services hereunder—so called “pass through costs”, including in particular costs of telephone connections,
faxes, internet, courier and mail services, accommodation and travel expenses of persons appointed to perform Services, which will be incurred in connection with the execution of the Agreement. These expenses will be invoiced on a monthly basis and
presented to the Sponsor with a detailed list. 

  

	 	b)	for any costs related to use of CRO company cars for business travels to and from study sites indicated by the Sponsor, 

  

	 	c)	for any other costs necessary for the proper conduct of the Study provided that such expenses have been pre-approved by the Sponsor. 


 

	6.	 Specification of expected costs and expenses (so called „pass through costs”) is included in Attachment No. 6 hereto. In case if costs,
expenses or a scope of Services connected with the conduct of the Study appear to be higher than those anticipated on the Agreement date, the Sponsor undertakes an obligation to cover these costs and reimburse CRO for expenses incurred




  

			
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in relation to the execution of the Agreement provided that such expenses have been pre-approved by the Sponsor. 


 

	7.	When CRO is in charge of investigators, sites, Study subject or IRB/EC fees or expenses payment or reimbursement, estimated or known amounts for such payments/reimbursements will be invoiced to the Sponsor, before
paying such fees or expenses. The CRO has no obligation to advance funds and make these payments unless and until the funds are received from the Sponsor. If Sponsor does not provide funds in time to enable CRO to make timely payments, Sponsor
agrees to be liable for and to reimburse CRO for any interest and other charges, costs, fees and expenses incurred by CRO because of such late payment. Any excess funds paid to CRO for such fees and expenses shall be refunded to Sponsor at the end
of the Study or sooner, upon Sponsor’s request. 

  

	8.	Sponsor is obliged to reimburse CRO for the costs and expenses incurred by CRO in relation to the execution of the Agreement within 30 days from the receipt of relevant documentary evidence supporting such costs and
expenses from CRO. 

  

	9.	Payment of the remuneration and reimbursement of costs incurred by CRO shall be made by a transfer to CRO bank account indicated on the invoice. 


 

	10.	CRO rates included in the budget in Attachment 6 shall automatically increase each calendar year beginning from January 1, 2015 for the next 12 month period, according to year inflation rate published by Eurostat,
the Statistical Office of the European Communities. The Parties agree that increase of rates shall be effective from the beginning of calendar year regardless of the date of publishing year inflation rate by Eurostat. 


§ 6. Confidentiality 
  

	1.	The CRO shall keep confidential any and all information and data concerning Sponsor`s business or its activities (including reports and information as well as all clinical data about the Study or its progress produced
by the CRO or the sites within the framework of this Agreement), or information obtained that may come to the knowledge of the CRO, its personnel or appointed representatives during or in connection with the execution of this Agreement including
without limitation third party confidential information received by the Sponsor (“Sponsor’s Confidential Information”). For the avoidance of any doubt, the Protocol, the Investigational Medicinal Product, the Study results, and the
Inventions (as defined below) shall be considered the Sponsor’s Confidential Information. 


  

			
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	2.	Sponsor shall keep confidential any and all information and data concerning the CRO`s business or its activities (including information produced by Sponsor within the framework of this Agreement) or information obtained
that may come to the knowledge of Sponsor, its personnel or appointed representatives during or in connection with the execution of this Agreement, and is not considered Sponsor’s Confidential Information. 


 

	3.	Parties undertake an obligation to keep strictly confidential any confidential information or data which came into possession of the other Party in any manner, were delivered or otherwise disclosed to the other Party in
connection with the Agreement. Parties may use and make the above mentioned information available solely for the purpose of the execution of the Agreement. 

  

	4.	The above provision does not apply to information which the receiving Party can demonstrate that: 

  

	 	a)	is known to the receiving Party at the moment of its disclosure, 

  

	 	b)	is publicly accessible at the time of its disclosure to the receiving Party or it becomes later publicly accessible without the Party’s fault, 


 

	 	c)	may be disclosed upon the other Party’s consent expressed in writing otherwise being void, 

  

	 	d)	was disclosed to the receiving Party by a third party that was not obliged to keep it confidential or 

  

	 	e)	is disclosed by virtue of laws in force. 

  

	5.	If confidential information needs to be disclosed to a third party for the purpose of performance hereof, the Sponsor or CRO, prior to making any such disclosure, will cause such third party to undertake the
confidentiality and non-use obligations in writing at least to the extent applicable to themselves under the Agreement. Any publication of data from the Study or oral presentations on an individual basis with respect to the Study data shall be
subject to the Sponsor’s prior review and approval. The Sponsor is entitled at its sole discretion to delay or reject of such publication due to Sponsor’s business or operational reasons. 


§ 7. Personal data processing 
  

	1.	 Sponsor undertakes to observe the provisions of Personal Data Protection Act of 29th of August 1997 (uniform text: Journal of Laws from 2002,
No. 101, position 926 with later changes) as well as secondary regulations, regarding personal data of CRO’s employees, contractors and other individuals (such as employees of CRO’s contractors), provided by CRO to Sponsor, in




  

			
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the scope of performance the obligations under the Agreement. The personal data of the CRO’s employees, contractors and other individuals will be processed by Sponsor on grounds of their
consent or justified purposes of a data controller. However, for the purposes of processing by Sponsor of the personal data of the CRO’s employees or contractors in relation to the execution of obligations of CRO as an employer, CRO entrusts
Sponsor with the processing of such personal data in accordance with the Agreement. 

  

	2.	Sponsor appoints CRO as its representative within the meaning of article 31a of the Personal Data Protection Act. 

  

	3.	The scope of the entrusted personal data includes the following categories: names, surnames, addresses, contact details, professional experience, current and past position, education, skills. Sponsor undertakes to
process the personal data by collecting, recording, storing, deleting compiling, amending, transferring in paper form and by electronic means. 

  

	4.	Sponsor cannot use entrusted personal data for any other purpose or in any other manner than necessary to execute the Agreement. Sponsor is also obliged neither to disclose nor to pass on the personal data to any entity
without prior written CRO’s consent. 

  

	5.	Sponsor is liable for the damages caused to CRO or any third party in the result of personal data processing against the Agreement by Sponsor or under its responsibility. 


 

	6.	When the Agreement is finished/terminated/expired, Sponsor is obliged to finish personal data processing, return or destroy all received documents and their copies, and return all received electronic data mediums to
CRO. 

  

	7.	Sponsor entrusts CRO with the processing of personal data of the investigators and the members of study teams for the purposes of the performance of activities connected with the conduct of the Study. The scope of the
entrusted personal data includes the following categories: names, surnames, addresses, place of work, telephone numbers, e-mail addresses, bank account numbers, PESEL numbers, tax identification numbers, professional experience, current and past
position, education. CRO undertakes to process the personal data by collecting, recording, storing, deleting, compiling, amending, transferring in paper form and by electronic means. Sponsor hereby authorizes CRO to subcontract the processing of the
personal data to a further data processor as shall be agreed in advance by the Sponsor. 

  

	8.	CRO undertakes to observe the provisions of the Personal Data Protection Act and the secondary regulations. CRO cannot use the entrusted personal data for any other purpose or in any other manner than necessary to
execute the Agreement. 


  

			
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	9.	In relations between CRO and Sponsor acting as data controllers / data processors towards each other, the following rules shall apply accordingly: 


 

	 	a)	the data processor is hereby obliged, prior to commencing the processing of the personal data and afterwards, during the term of this Agreement, to apply any technical and organizational measures that will ensure the
security of the personal data being processed, as set forth in the Personal Data Protection Act and the secondary regulations, and any legislation that will supplement and/or replace them in the future; in particular, it should secure the personal
data against access by unauthorized persons, its removal by unauthorized persons, and against it being damaged or destroyed; 

  

	 	b)	the data processor shall be obliged to ensure supervision of the following: when and by whom the personal data has been entered into the data filing system and to whom the data has been transferred; 


 

	 	c)	the data processor undertakes to preserve the confidentiality of the personal data entrusted to it under this Agreement; 

  

	 	d)	only persons who were authorized by the data processor shall be allowed to carry out the processing of personal data; 

  

	 	e)	the data processor shall be obliged to take all necessary steps to ensure that the persons referred to in point (d) of this clause keep the personal data and the methods of their protection confidential;


  

	 	f)	the data processor shall immediately inform the data controller of any instance of any breach, whatsoever, of the security of the personal data entrusted to the data processor and processed under this Agreement;


  

	 	g)	the data processor shall grant the data controller, at its request, any necessary information concerning all personal data processed by the data processor; 


 

	 	h)	the data controller shall have the right to conduct inspections as to whether the data processor is observing the principles of processing the personal data specified in the Personal Data Protection Act, the secondary
regulations and this Agreement, by accessing and inspecting any premises where the personal data is processed, as well as the documents, equipment and IT systems relating to the personal data processing; 


 

	 	i)	 the data controller shall be entitled to review whether the above principles of the processing of the personal data are being observed and as such the
data controller’s representatives will be entitled to demand that the data processor’s representatives provide to the data controller 



  

			
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the necessary information concerning the way in which the data processor processes the personal data contained in the data filing system; 


 

	 	j)	any inspection of whether the above principles of the personal data processing are being observed may only take place after the data controller has notified the data processor of the intention of carrying out such an
inspection at least two days in advance of the date of the commencement of the inspection, and has indicated in writing the persons designated to carry out the inspection; an inspection may be exercised by the data controller at the location where
the personal data are being processed – between the hours of 9 a.m. and 4 p.m. on any business day; 

  

	 	k)	following the inspection, the data controller may draw up recommendations concerning the improvement of the quality of the safeguarding of the personal data, as well as the means of its processing by the data processor
and the means of remedying any identified irregularities, which the data processor is obliged to immediately remedy not later than 30 days after the data controller’s notification of its observations; 


 

	 	l)	upon the expiry or termination of this Agreement the data processor shall be obliged to transfer the personal data to the data controller or delete all the personal data, within seven days of receiving the data
controller’s instruction; the deletion of the personal data shall be understood as the erasing of the personal data, or their modification in such a way that the identity of the persons to whom the data refers cannot be established.


 § 8. Intellectual property 
  

	1.	The Parties acknowledge that all rights to materials, Investigational Medicinal Product, data bases, notes, analyses, lists, studies or any other documents, as well as names and graphic signs made available to CRO by
the Sponsor in any manner whatsoever, shall remain the property of the Sponsor and CRO shall not acquire any rights thereto, except for the right of use thereof during execution of the Agreement for the purpose of conducting the Study in the manner
permitted by the Sponsor. 

  

	2.	 Inventions or discoveries whether or not patentable, processes, trade secrets, data, improvements, and/or patents relating to the Investigational
Medicinal Product or otherwise arising from the Study, conceived, generated, developed or first reduced to practice, as the case may be, during the term of this Agreement (hereinafter called “Inventions”), either by the CRO,




  

			
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its employees, sites, investigator or any other Sub-contractors related to this Agreement shall be the property of the Sponsor. 


 

	3.	The CRO its employees, sites, investigator or any other Sub-contractors will promptly inform Sponsor of any Invention or discovery arising from the Study, and assign its rights in relation to all intellectual property
rights and know how, and provide reasonable assistance to the Sponsor in filing or prosecuting intellectual property rights, at the expense of the Sponsor. 


§ 9. Duration of the Agreement and its termination 
  

	1.	The Agreement is concluded for a specified period of time and shall be valid from the Effective Date until the termination of the Study unless any circumstances indicated below should occur. 


 

	2.	Each Party has a right to terminate the Agreement with immediate effect in case of a material breach by the other Party of the obligations resulting from the Agreement if a default is not cured within 30 (thirty) days
from the date of delivery of a written notice on the discovered breach to the other Party. 

  

	3.	The Sponsor has a right to terminate the Agreement upon 90 days’ written notice without giving cause and CRO has a right to terminate the Agreement upon 120 days’ written notice without giving cause.


  

	4.	Upon receipt of the notice of termination of the Agreement from the Sponsor by CRO or dispatch of the same to the Sponsor by CRO, CRO shall make all possible efforts to terminate or transfer further conduct of any
unfinished Services as soon as possible, according to the Sponsor’s instructions. In such a case, CRO shall cease to provide Services or undertake further obligations in connection with the Services unless Parties agreed otherwise in writing.


  

	5.	The Sponsor undertakes an obligation to reimburse CRO for all necessary and actual costs connected with the termination or expiration of the Agreement as well as to pay CRO due remuneration, in particular to reimburse
CRO for any expenses incurred (so called „pass through costs”) or to be incurred in relation to provision of the Services from which CRO cannot withdraw. Promptly after the date of the Agreement termination or expiration, CRO shall issue
an invoice for the above costs and expenses to the Sponsor. 


  

			
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 § 10. Non-Solicitation Clause 

 

	1.	The Sponsor undertakes an obligation that it shall not employ any employee of the CRO, in its own enterprise or in any company under its control, during the term of the Agreement and for the period of 2 years from the
date of termination or expiry hereof. 

  

	2.	In the event of employing the above mentioned persons, the Sponsor shall be obliged to pay a contractual fine in the amount of Euro 50 000 (say: fifty thousands) per each person employed within 7 days from the receipt
of the call for payment. Payment of contractual fine shall not deprive CRO of its right to claim damages exceeding the amount of the contractual fine reserved. 


§ 11. Final provisions 
  

	1.	Neither Party shall be liable to the other Party in connection with this Agreement for any indirect, consequential (including without limitation lost profits), incidental, special or punitive damages. 


 

	2.	CRO shall not bear any liability connected with the Investigational Medicinal Product, including liability for administering the Investigational Medicinal Product. CRO’s liability due to negligence, non-adherence
to professional standards or breach of the Agreement shall be limited to the double amount of the remuneration (CRO fee) received. 

  

	3.	Sponsor shall defend, indemnify, and hold harmless CRO, its affiliates and their respective directors, officers, employees, consultants, sub-contractors, independent contractors, and agents from and against any and all
losses, claims (including third party claims), actions, damages, liabilities, awards, costs and expenses (including reasonable legal counsel fees and expenses), whether joint or several, relating to or arising from or in connection with this
Agreement or the Services contemplated herein, including but not limited to, the Study, test, specifications, compound, device, placebo or Investigational Medicinal Product, potential product or procedure performed or administered as a result of the
Protocol and this Agreement or any litigation, investigation or other proceeding relating to any of the foregoing, unless as a result of CRO’s its affiliates and their respective directors, officers, employees, consultants, sub-contractors,
independent contractors, and agents negligence, non-adherence to professional standards or breach of the Agreement. 

  

	4.	CRO shall defend, indemnify, and hold harmless Sponsor, its affiliates and its and their respective directors, officers, employees, and agents from and against any and all losses, claims (including third party claims),
actions, damages, liabilities, costs and expenses (including 


  

			
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reasonable legal counsel fees and expenses) (“Sponsor Losses”) but only to the extent such Sponsor Losses are related to or arise from or in connection with CRO’s negligence,
non-adherence to professional standards or breach of this Agreement, except to the extent that such Sponsor Losses arise from (i) the negligence or reckless or willful act or omission of Sponsor, its affiliates or its and their respective
directors, officers, employees, contractors or agents; or (ii) any breach of this Agreement by Sponsor, its affiliates, or its and their respective directors, officers, employees, contractors or agents. 


 

	5.	The Party seeking indemnity will give the indemnifying party prompt written notice (within 15 days knowledge) of any matter upon which such indemnified party intends to base a claim for indemnification (an
“Indemnity Claim”). The indemnified party shall have the right to participate jointly with the indemnifying party, at its own expense, in the defense, settlement or other disposition of any Indemnity Claim. 


 

	6.	In no event shall either Party be liable to the other in case of not being able to perform its obligations hereunder due to a natural disaster, general strike, war, riots, fire, order of the authorities or any other
unforeseeable and unpreventable circumstances, provided that such Party unable to perform its obligation will do its best effort to fulfill its obligations. The Party affected by such circumstances shall immediately notify the other Party of this
fact in writing, providing any relevant information regarding the matter. 

  

	7.	No Party may assign any rights or obligations resulting from the Agreement to any third party without prior written consent of the other Party. 


 

	8.	Any representations of the Parties as specified herein shall be made in writing, otherwise null and void. 

  

	9.	Except for cases expressly indicated in the Agreement, all statements, notices, calls etc. connected with the Agreement must be delivered to the addresses of the Parties defined in the preamble hereof, otherwise void
and ineffective. Either Party should notify the other of the change of its address in accordance with this paragraph. Such notice shall be deemed properly served by the Party after its receipt by the addressee. All and any notices and statements
sent thus far in connection with this Agreement to the addresses given above shall be deemed as served effectively. 

  

	10.	Provisions of § 4, § 6, § 8 and § 10 of the Agreement shall remain in force despite its expiry or termination for any reason. 


 

	11.	 For the avoidance of doubt, this Agreement and the Protocol may only be amended by the agreement in writing of duly authorized signatories of Sponsor
and CRO, otherwise being null 



  

			
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and void. Changes in the Protocol may imply changes in the total course of the Study (costs, time-lines etc.). 


 

	12.	If any one or more provisions of this Agreement shall be found to be illegal or unenforceable in any respect, the validity, legality and enforceability of the remaining provisions shall not in any way be affected or
impaired thereby. 

  

	13.	The Agreement and any matters connected herewith shall be governed by the laws of England, excluding its rules for choice of law. Any dispute relating to or arising in connection with this Agreement, which is not
settled within a reasonable time, shall be finally settled under the Rules of Arbitration of the International Chamber of Commerce (“ICC”) by one arbitrator appointed in accordance with the said rules. The award shall be final and binding
and enforceable in any court of competent jurisdiction. The arbitration shall be held in London, United Kingdom, in English language. 

  

	14.	The Agreement has been drawn up in two identical counterparts, one counterpart for each of the Parties. 

  

			
	CRO:	  	Sponsor:
		
	Anna Baran /s/ Anna Baran	  	/s/ Amos Ron
	Mike Jagielski /s/ Mike Jagielski	  	Vascular Biogenics Ltd.
		  	Amos Ron
		  	January 1, 2014


  

			
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 Attachment No. 1 

Scope of Services: 

Part A 
 Study
Assumptions 
  

			
	 STUDY ASSUMPTIONS

	 Number of countries involved
	  	1
	 COUNTRIES INVOLVED
	  	Poland
	 CRA staff involved
	  	3
	 STUDY SITES
	  	10
	 PATIENTS ENROLLED (# of expected)
	  	50
	 NUMBER OF PATIENT’s VISITs IN SITE DURING THE STUDY
	  	9
	 PLANNED NUMBER OF PAYMENTS FOR PI AND SITES DURING THE STUDY
	  	3


  

			
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 Attachment No. 1 

Scope of Services: 
 Part
B 
 Division of Responsibilities CRO—Sponsor 
  

							
	 	  	KCR	  	VBL
Ltd.	  	 Comments

	STUDY INITIATION	  		  		  	
				
	Protocol development	  		  	X	  	
				
	Protocol review	  	X	  	X	  	KCR to review the draft of study protocol and provide VBL with comments.
				
	Protocol approval	  		  	X	  	
				
	Protocol printing	  	X	  		  	
				
	Protocol distribution to sites	  	X	  		  	
				
	Preparation of amendments	  		  	X	  	
				
	CRF design and development (e CRF)	  		  	X	  	
				
	CRF review & approval	  		  	X	  	
				
	Preparation of master Informed Consent (IC) and Patient Information Sheet (PIS)	  		  	X	  	
				
	Revision and translation of Informed Consent and Patient Information Sheet according to local Ethical Committee requirements	  	X	  		  	
				
	Final approval of country specific IC and PIS	  		  	X	  	Based on back translation of local of Informed Consent and Patient Information Sheet. Approval process according to KCR SOP.
				
	Monitoring Plan development	  	X	  		  	
				
	Monitoring Plan approval	  		  	X	  	
				
	Recruitment Plan development	  	X	  		  	
				
	Trial Master File Set-up	  	X	  		  	
				
	Distribution of Site Documents	  	X	  		  	
				
	Randomization schedule preparation	  	X	  		  	


  

			
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	 	  	KCR	  	VBL
Ltd.	  	 Comments

	REGULATORY / ETHICS COMMITTEE SUBMISSIONS	  		  		  	
				
	Preparation of the documentation for Ethics Committees	  	X	  	X	  	 VBL to provide:
 - Investigator’s
Brochure
 - IMPD
 - CRF

- Insurance certificate
 - Patient related scales/diaries

- Certificate of analysis
 - Drug label

- Manufacturing authorisation
 - GMP certificate

KCR to provide VBL with country specific requirements regarding submission and to prepare submission package.

				
	Submission of the documentation for Ethics Committees and follow up until authorisation	  	X	  		  	
				
	Preparation of the documentation for Regulatory Authorities	  	X	  	X	  	 VBL to provide:
 - Investigator’s
Brochure
 - IMPD
 - CRF

- Insurance certificate
 - Patient rated scales/diaries -
Certificate of analysis

				
		  	X	  	X	  	 - Drug label
 - Manufacturing authorisation

- GMP certificate
 KCR to provide VBL with country specific
requirements regarding submission and to prepare submission package.

				
	Submission of the documentation for Regulatory Authorities and follow up until authorisation	  	X	  		  	


  

			
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	 	  	KCR	  	VBL
Ltd.	  	 Comments

	TRANSLATIONS	  		  		  	
				
	Translations	  	X	  		  	Relevant for patient-related documents, labels, Power of Attorney
				
	SITE RECRUITMENT AND INITIATION	  		  		  	
				
	Investigator’s Site Identification	  	X	  		  	
				
	Investigator’s Site Selection	  	X	  		  	
				
	Final Site Selection	  	X	  	X	  	 KCR to provide VBL with pre-study visit reports and lists of recommended sites in all selected countries.

VBL to approve selected sites.

				
	Conduct Site Selection Visits	  	X	  		  	
				
	Negotiate Investigators/Sites Contracts	  	X	  		  	
				
	Final Approval for Investigators/Sites Contracts	  		  	X	  	
				
	Signature on Investigators/Sites Contracts	  	X	  		  	
				
	Regulatory Documents collection & review	  	X	  		  	
				
	Conduct Site Initiation Visits	  	X	  		  	
				
	INVESTIGATOR MEETING	  		  		  	
				
	Investigator’s Meeting Planning	  	X	  		  	
				
	Investigator’s Meeting Preparation	  	X	  	X	  	 VBL to present:
 - VB-201: Scientific
Background
 - Phase I/II Experience & Development Plan
 -
Study Design & Objectives
 - Protocol Overview
 -
Eligibility Criteria
 - Study Specific Procedures
 - Study
Assessment Scales
 KCR to present:
 - Communication Plan

- Timelines & Recruitment Strategies
 - ICH GCP
Refreshment

				
	Investigator’s Meeting Attendance	  	X	  	X	  	


  

			
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	 	  	KCR	  	VBL
Ltd.	  	 Comments

				
	STUDY DRUG MANAGEMENT/CENTRAL LABORATORY MANAGEMENT	  		  		  	
				
	Clinical Trial Supply Logistics Management	  		  	X	  	
				
	Packaging and labeling of study medication	  		  	X	  	
				
	Distribution of study medication to sites	  		  	X	  	
				
	Destruction of unused supplies	  		  	X	  	
				
	Randomization list management	  		  	X	  	
				
	Central Laboratory Supplies and Logistic Set-up/Courier Management	  		  	X	  	By VBL subcontractor.
				
	Central Laboratory Management	  		  	X	  	VBL subcontractor to manage the central laboratory.
				
	STUDY MONITORING	  		  		  	
				
	Conduct Site Monitoring Visits	  	X	  		  	
				
	Communication with Sites	  	X	  		  	
				
	Monitoring visit reports preparation and review	  	X	  		  	
				
	Monitoring visit reports final approval	  		  	X	  	
				
	S.D.V.: (100% of patients, 100% of key study parameters)	  	X	  		  	
				
	Periodic Regulatory Document Collection / Updates (Investigator’s Master File management)	  	X	  		  	
				
	Data review/correction on all CRF’s	  	X	  		  	
				
	Resolution of Queries with Sites	  	X	  		  	
				
	SAE Reconciliation with Sites	  	X	  		  	
				
	Conduct Site Close-out / Termination Visits	  	X	  		  	
				
	Drug accountability during study and final drug record reconciliation	  	X	  		  	
				
	End of Study Notification to Regulatory Agencies/ECs	  	X	  		  	


  

			
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	 	  	KCR	  	VBL
Ltd.	  	 Comments

	CLINICAL STUDY MANAGEMENT	  		  		  	
				
	Maintain Central Trial Master File	  	X	  		  	
				
	Fortnightly enrolment updates and Weekly Status Reports to Sponsor	  	X	  		  	
				
	Administered Investigator’s Payments	  	X	  		  	KCR will be responsible for bank transfers.
				
	Prepare and Distribute Newsletter (if applicable)	  		  	X	  	
				
	Central File Archiving	  		  	X	  	
				
	Clinical Team Communication	  	X	  		  	KCR to provide Communication Plan.
				
	MEDICAL MONITORING	  		  		  	
				
	Development of Medical Monitoring Plan	  		  	X	  	
				
	Provide Medical Oversight to CRO Project Team	  		  	X	  	
				
	Medical Communication/Consultation with Sites	  		  	X	  	
				
	Patient Eligibility - Medical Review	  		  	X	  	
				
	Review Safety Data Listing	  		  	X	  	
				
	Review CRFs for safety/efficacy	  		  	X	  	
				
	Review Safety Laboratory Data	  		  	X	  	
				
	Review of Data Management Coding	  		  	X	  	
				
	Review of Data Management SAE reconciliation	  		  	X	  	
				
	Organization of Data Safety Monitoring Board Meeting	  		  	X	  	
				
	SAFETY MONITORING	  		  		  	
				
	Safety Plan Preparation	  		  	X	  	
				
	SAE Reporting Procedure and Database Set-up	  		  	X	  	
				
	Receipt & Review of Initial SAE Report from Site	  	X	  		  	
				
	Tracking /Analyzing SAE Report	  		  	X	  	
				
	Entering SAE into Database	  		  	X	  	
				
	Writing SAE Narrative	  		  	X	  	
				
	Expectedness Judgment for SAE & Regulatory Reporting Assessment	  		  	X	  	
				
	Final Medical and Regulatory Judgment	  		  	X	  	
				
	Preparing Annual Report for Competent Authority in EU (inc. safety update)	  		  	X	  	
				
	Reporting Expedited SAEs to Regulatory Authorities	  		  	X	  	
				
	Reporting Expedited SAEs to Investigators and EC	  	X	  		  	
				
	Ongoing SAE File Maintenance	  		  	X	  	


  

			
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	 	  	KCR	  	VBL
Ltd.	  	 Comments

	DATA MANAGEMENT	  		  		  	
				
	Preparation of Data Management Documentation such as Data Management Plan, Data Review Plan, Data Handling Guiding	  		  	X	  	
				
	EDC collector development	  		  	X	  	
				
	Data Review, Query Generation	  		  	X	  	
				
	Query Resolution	  	X	  		  	
				
	Import of Electronic (Laboratory) Data	  		  	X	  	By VBL subcontractor
				
	Reconciliation of SAEs	  		  	X	  	
				
	Provision of data extracts during study to support interim analyses	  		  	X	  	
				
	Documentation Maintenance	  		  	X	  	
				
	Archiving of EDC tool, Archiving of Data Management Material	  		  	X	  	
				
	STATISTICS AND REPORTING	  		  		  	
				
	Development of Statistical Analysis Plan	  		  	X	  	
				
	Final Approval for Statistical Analysis Plan	  		  	X	  	
				
	Creation of Analysis Dataset (Statistical analysis of the dataset)	  		  	X	  	
				
	Programming of Tables, Figures and Listings	  		  	X	  	
				
	PK parameters calculation	  		  	X	  	
				
	Development of interim and final Integrated Statistical/Clinical Report in conformity to ICH guideline and CTD	  		  	X	  	
				
	Review of final Integrated Statistical/Clinical Report in conformity to ICH guideline and CTD	  		  	X	  	
				
	Final Approval for clinical Study Report	  		  	X	  	
				
	Writing of SAE and AE Discontinuation Narratives	  		  	X	  	
				
	AUDITS	  		  		  	
				
	Conduct of GCP Audits of Investigator’s Sites	  	X	  		  	
				
	Conduct of Quality Assurance Audit of Database	  		  	X	  	
				
	PROJECT MANAGEMENT	  		  		  	
				
	Management of the study team	  	X	  		  	
				
	Communication with study sponsor and vendors	  	X	  		  	
				
	Coordination of start-up activities, realization phase and closure	  	X	  		  	
				
	Oversees the regulatory document collection and submission process.	  	X	  		  	
				
	Control and track the budget monthly and cumulative realization	  	X	  		  	
				
	Preparation of Risk Management Plan and/or Contingency Plan, if required	  	X	  		  	
				
	CONTRACTS AND PAYMENTS	  		  		  	
				
	Preparation of study contracts	  	X	  		  	
				
	Signature and payments	  	X	  	X	  	
				
	Payment of Ethics Committees’ fees	  	X	  		  	


  

			
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 Attachment No. 2 

Timelines 
 STUDY
TIMELINES 
  

					
	[***]	  	 	[***]	  


  

			
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	Protocol VB-201-079	  	VB-201

  

 Attachment No. 3 

Study Protocol 

CLINICAL PROTOCOL 
  

			
	Title:	  	A Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral VB-201 in Patients with Moderate to Severe Plaque Psoriasis
		
	Protocol No.	  	VB-201-079
		
	Eudra CT No.:	  	2012-002763-10
		
	Investigational	  	VB-201
	Product:	  	
		
	Indication:	  	Plaque Psoriasis
		
	Development	  	2
	Phase:	  	
		
	Sponsor:	  	Vascular Biogenics Ltd.
		  	6 Jonathan Netanyahu St.
		  	Or Yehuda, Israel 60376
		  	Phone: 972-3-6346450
		  	Fax: 972-3-6346449
		
	Version:	  	2.2 (Poland and Israel only)
		
	Date:	  	December 2, 2013

 CONFIDENTIAL 

This document contains proprietary and confidential information of VBL. Acceptance of this document constitutes agreement by the recipient that no previously
unpublished information contained herein will be published or disclosed without the prior written approval of Vascular Biogenics Limited with the exception that this document may be disclosed to study personnel under your supervision who need to
know the contents for conducting the study and appropriate Institutional Review Boards (IRBs)/Ethics Committees (IEC) under the condition that the personnel have agreed to keep this information confidential. The foregoing shall not apply to
disclosure required by governmental regulations or laws, however, VBL shall be promptly notified of any such disclosure. 

  

			
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	Protocol VB-201-079	  	VB-201

  

 AUTHOR SIGNATURE PAGE 

The undersigned have written, reviewed and approved the following protocol: 
  

					
	Ron Goldblum, MD	  	 /s/ Ron Goldblum
	  	 02 DEC 2013

	Medical Monitor	  	Signature	  	Date
	Vascular Biogenics Ltd	  		  	
			
	Naamit Sher, PhD	  	 /s/ Naamit Sher
	  	 3 Dec 2013

	Vice President	  	Signature	  	Date
	Drug Development & RA	  		  	
	Vascular Biogenics Ltd	  		  	


  

			
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	Protocol VB-201-079	  	VB-201

  

 CONFIDENTIALITY AND INVESTIGATOR STATEMENT 

Vascular Biogenics Limited 

Clinical Research Protocol 

VB-201-079 
 The information contained in
this document and all information provided to you related to VB-201 (“drug”) are the confidential and proprietary information of Vascular Biogenics Limited (Sponsor) and except as may be required by federal, state or local laws or
regulations, may not be disclosed to others without prior written permission of Sponsor. The Principal Investigator may, however, disclose such information to supervised individuals working on the Drug, provided such individuals agree to be bound to
maintain the confidentiality of such Drug information. 
 I agree to abide by the statement of confidentiality. 

I agree to conduct the study according to this protocol and have read and agree to comply with the Investigator’s Responsibilities. Any changes in
procedure will only be made if necessary to protect the safety, rights, or welfare of subjects. 
 I agree to comply with the current International
Conference on Harmonisation (ICH) Guideline on Good Clinical Practice (GCP), applicable laws and regulations, and the Declaration of Helsinki. 
 I agree to
conduct the Study in person or to supervise the Study. 
 I agree to ensure that all who assist me in the conduct of the Study have access to the Study
protocol and any amendments and are aware of their obligations. 

					
	  
	  	  

	Principal Investigator	  	Date (dd/mmm/yyyy)
		
	Printed Name:	  	  

		
	Institution:	  	  

		
	Address:	  	  



  

			
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	Protocol VB-201-079	  	VB-201

  

 TABLE OF CONTENTS 

 

									
	1.0	  	STUDY SYNOPSIS	  	 	31	  
			
	2.0	  	LIST OF ABBREVIATIONS	  	 	44	  
			
	3.0	  	INTRODUCTION	  	 	46	  
				
		  	3.1	  	Psoriasis: Pathophysiology and Unmet Medical Need	  	 	46	  
				
		  	3.2	  	Name and description of the investigational product	  	 	46	  
				
		  	3.3	  	Summary of findings from nonclinical studies relevant to the trial	  	 	46	  
				
		  	3.4	  	Summary of findings from clinical studies	  	 	48	  
				
		  		  	3.4.1     VB-201 Phase I Studies	  	 	48	  
				
		  		  	3.4.2     VB-201 Phase II studies	  	 	48	  
				
		  	3.5	  	Rationale for Route of Administration, Pharmaceutical Form, Dosage, Dosage Regimen and Treatment Period	  	 	50	  
				
		  	3.6	  	Rationale for the PASI 50 Endpoint	  	 	50	  
				
		  	3.7	  	Rationale for the Use of Placebo	  	 	51	  
			
	4.0	  	OBJECTIVES	  	 	52	  
				
		  	4.1	  	Safety Objective	  	 	52	  
				
		  	4.2	  	Efficacy Objective	  	 	52	  
				
		  	4.3	  	Exploratory Biomarker	  	 	52	  
			
	5.0	  	INVESTIGATIONAL PLAN	  	 	52	  
				
		  	5.1	  	Study Design	  	 	52	  
				
		  	5.2	  	Number of Patients	  	 	52	  
				
		  	5.3	  	Subject Selection	  	 	54	  
				
		  		  	5.3.1     Inclusion Criteria	  	 	54	  
				
		  		  	5.3.2     Exclusion Criteria	  	 	54	  
				
		  	5.4	  	Subject Screening and Randomization	  	 	56	  
				
		  	5.5	  	Duration of Participation	  	 	56	  
				
		  	5.6	  	Protocol Amendments	  	 	56	  
				
		  	5.7	  	Withdrawal Criteria	  	 	56	  
				
		  	5.8	  	Study/Study Site Termination	  	 	57	  
			
	6.0	  	STUDY DRUG	  	 	57	  
				
		  	6.1	  	Formulation, Packaging, and Labeling	  	 	57	  
				
		  	6.2	  	Storage and Handling	  	 	58	  
				
		  	6.3	  	Accountability	  	 	58	  


  

			
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	Protocol VB-201-079	  	VB-201

  


									
				
		  	6.4	  	Access to Blinded Treatment	  	 	58	  
				
		  	6.5	  	Administration of Study Drug	  	 	59	  
				
		  		  	6.5.1     Dosage	  	 	59	  
				
		  		  	6.5.2     Assignment of Treatment Cartons	  	 	60	  
				
		  		  	6.5.3     Compliance	  	 	60	  
			
	7.0	  	PRIOR AND CONCOMITANT MEDICATION	  	 	60	  
			
	8.0	  	OUTCOME MEASURES	  	 	61	  
				
		  	8.1	  	Efficacy Assessments	  	 	61	  
				
		  	8.2	  	Safety Assessments	  	 	64	  
				
		  		  	8.2.1     Physical Examination Assessments	  	 	64	  
				
		  		  	8.2.2     Clinical Laboratory & Other Safety Assessments	  	 	64	  
				
		  		  	8.2.3     Population Pharmacokinetics	  	 	65	  
				
		  		  	             8.2.3.1     Blood and Urine Samples	  	 	66	  
				
		  		  	             8.2.3.2     Risk Assessment	  	 	66	  
				
		  		  	8.2.4     Study Withdrawals	  	 	66	  
				
		  		  	8.2.5     Adverse Events and Serious Adverse Events	  	 	66	  
				
		  	8.3	  	Exploratory Assessments	  	 	66	  
				
		  		  	8.3.1     Inflammatory Related Biomarkers	  	 	67	  
			
	9.0	  	SCHEDULE OF STUDY ASSESSMENTS	  	 	67	  
				
		  	9.1	  	Screening Visit	  	 	67	  
				
		  	9.2	  	Baseline	  	 	67	  
				
		  	9.3	  	Week 2	  	 	68	  
				
		  	9.4	  	Week 4, 8, 12	  	 	69	  
				
		  	9.5	  	Week 16	  	 	69	  
				
		  	9.6	  	Week 20	  	 	70	  
				
		  	9.7	  	Week 24/ Early Termination	  	 	70	  
				
		  	9.8	  	Week 28	  	 	71	  
			
	10.0	  	ADVERSE EVENTS	  	 	71	  
				
		  	10.1	  	Definition of Adverse Event	  	 	71	  
				
		  	10.2	  	Definition of Serious Adverse Event	  	 	72	  
				
		  	10.3	  	Reporting and Documentation	  	 	73	  
				
		  	10.4	  	Patient Stopping Rules	  	 	74	  
				
		  	10.5	  	Pregnancy	  	 	75	  
			
	11.0	  	STATISTICAL CONSIDERATIONS	  	 	75	  


  

			
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	Protocol VB-201-079	  	VB-201

  


											
				
		  	11.1	  	Statistical Methods	  	 	75	  
					
		  		  	11.1.1	  	Comparisons of Interest	  	 	75	  
					
		  		  	11.1.2	  	Sample Size Determination	  	 	75	  
					
		  		  	11.1.3	  	Subject Population/Data Sets To Be Evaluated	  	 	75	  
				
		  		  	              11.1.3.1       Modified Intent-To-Treat (MITT) Population	  	 	75	  
				
		  		  	              11.1.3.2       Per-Protocol Population	  	 	76	  
				
		  		  	              11.1.3.3       Safety Population	  	 	76	  
					
		  		  	11.1.4	  	Randomization	  	 	76	  
				
		  	11.2	  	Statistical Analyses	  	 	76	  
					
		  		  	11.2.1	  	Subject Disposition	  	 	77	  
					
		  		  	11.2.2	  	Demography	  	 	77	  
					
		  		  	11.2.3	  	Efficacy Analysis	  	 	77	  
				
		  		  	              11.2.3.1       Primary Efficacy Endpoints	  	 	77	  
				
		  		  	              11.2.3.2       Secondary Efficacy Endpoints
	  	 	78	  
				
		  		  	              11.2.3.3       Tertiary Endpoints	  	 	79	  
					
		  		  	11.2.4	  	Safety Analysis	  	 	80	  
				
		  		  	              11.2.4.1       Adverse Events	  	 	80	  
				
		  		  	              11.2.4.2       Laboratory Parameters	  	 	80	  
				
		  		  	              11.2.4.3       Vital Signs	  	 	81	  
				
		  		  	              11.2.4.4       Withdrawals	  	 	81	  
				
		  		  	              11.2.4.5       Deaths	  	 	81	  
				
		  		  	              11.2.4.6       Dropouts	  	 	81	  
					
		  		  	11.2.5	  	Concomitant Medications	  	 	81	  
			
	12.0	  	DATA RECORDING, MONITORING, AND RETENTION	  	 	81	  
				
		  	12.1	  	Source Documents	  	 	81	  
				
		  	12.2	  	Case Report Forms (CRFs)	  	 	81	  
				
		  	12.3	  	Record Retention	  	 	81	  
				
		  	12.4	  	Monitoring Requirements	  	 	82	  
				
		  	12.5	  	Subject Confidentiality	  	 	82	  
			
	13.0	  	ETHICS	  	 	83	  
				
		  	13.1	  	Ethical Conduct of the Study	  	 	83	  
				
		  	13.2	  	Local Regulatory Approval	  	 	83	  
				
		  	13.3	  	Ethics Committee Approval	  	 	84	  
				
		  	13.4	  	Subject Information and Informed Consent	  	 	84	  


  

			
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	 14.0         PUBLICATION
	  	 	85	  
		
	 15.0         LIST OF APPENDICES
	  	 	85	  
		
	 16.0         REFERENCES
	  	 	87	  
	
	LIST OF TABLES	  
		
	 Table 1: Schedule of Procedures for VB-201-079 (Psoriasis)
	  	 	42	  
		
	 Table 2. Composition of the patient identification number
	  	 	53	  
		
	 Table 3. Composition of the randomization number
	  	 	53	  
		
	 Table 4. VB-201 Drug Distribution
	  	 	59	  
		
	 Table 5. Clinical Assessments Relating to Efficacy
	  	 	62	  
		
	 Table 6. Physical Examination Assessments Relating to Safety
	  	 	64	  
		
	 Table 7. Clinical Laboratory & Other Assessments Relating to Safety
	  	 	65	  
		
	 Table 8. Population Pharmacokinetics
	  	 	66	  
		
	 Table 9. Clinical Laboratory for Exploratory Assessments
	  	 	66	  


  

			
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 1.0         STUDY SYNOPSIS 

 

			
	Title of Study:	  	A Randomized, Double-Blind, Dose-Ranging, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Oral VB-201 in Patients with Moderate to Severe Plaque Psoriasis
		
	Sponsor:	  	VBL
		
	Phase:	  	Phase 2
		
	Patient Population:	  	Male or female patients >18 to <75 of age with moderate to severe, stable, active plaque Psoriasis Vulgaris affecting between 10% to 30% of the body surface and with a Psoriasis Area and Severity Index (PASI)
score of 10 to 20
		
	Efficacy Objective:	  	To examine the effect of treatment with two different doses of VB-201 compared to placebo for 16 weeks and 24 weeks on measures of disease activity in patients with psoriasis.
		
	Safety Objective:	  	To examine the safety and tolerability of up to 24 weeks’ treatment with VB-201 vs. placebo in patients with psoriasis.
		
	Study Design:	  	[***]


  

			
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	Dosage Regimen and Treatment Groups	  	[***]
		
	Investigative Product Name and Description	  	[***]
		
	Number of Subjects:	  	;[***]
		
	Duration of Participation:	  	[***]


  

			
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	Eligibility Criteria Inclusion Criteria	  	[***]
		
	Exclusion Criteria	  	[***]


  

			
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		  	4. [***]


  

			
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		  	[***]
		
	Concomitant	  	[***]


  

			
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	Medications:	  		  	[***]
			
	Safety Endpoints:	  		  	[***]
			
	Stage 1 Primary Efficacy Endpoint:	  		  	[***]
			
	Stage 1 Secondary Endpoints:	  	1.	  	[***]


  

			
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	Protocol VB-201-079	  	VB-201

  


					
		  		  	[***]
			
	Stage 1 Tertiary Endpoints:	  	1.	  	[***]


  

			
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	Stage 2 Primary Efficacy Endpoint:	  		  	[***]


  

			
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	 Stage 2 Secondary

Endpoints:
	  	1.	  	[***]
			
	 Stage 2 Tertiary

Endpoints:
	  	1.	  	[***]


  

			
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	Protocol VB-201-079	  	VB-201

  


					
			
		  	4.	  	[***]
			
	Compliance Measures	  		  	[***]
			
	Study Conduct	  		  	[***]
			
	Statistical Methods	  		  	[***]


  

			
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	Rationale for Number of Subjects:	  		  	    [***]


  

			
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 Table 1: Schedule of Procedures for VB-201-079 (Psoriasis) 

 

																			
	Evaluation	  	[***]	 	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]
	 	  	 	 	 	STAGE 1	 	STAGE 2
	 Study Day
	  	 	[	***] 	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]
	 Assessment Window (±Days)
	  				 		 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]
	 Informed Consent
	  	 	X	  	 		 		 		 		 		 		 	
	 Inclusion/ Exclusion Criteria
	  	 	X	  	 	X	 		 		 		 		 		 	
	 [***]
	  	 	X	  	 		 		 		 		 		 		 	
	 [***]
	  	 	X1	  	 	X	 		 		 	X	 		 	X	 	
	 [***]
	  	 	X	  	 	X	 		 		 	X	 		 	X	 	
	 [***]
	  	 	X	  	 	X	 		 	X	 	X	 	X	 	X	 	(X)3
	 [***]
	  				 	X	 		 	X	 	X	 	X	 	X	 	
	 [***]
	  				 	X	 		 	X4	 	X	 		 	X	 	
	 [***]
	  	 	X	  	 		 		 		 	X	 		 	X	 	
	 [***]
	  	 	X5	  	 	X6	 		 		 	X	 		 	X	 	
	 [***]
	  	 	X	  	 	X7	 		 	X	 	X	 	X	 	X	 	X
	 [***]
	  				 	X	 		 	X	 	X	 	X	 		 	
	 [***]
	  				 		 		 	X	 	X	 	X	 	X	 	
	 [***]
	  				 		 		 	X	 	X	 	X	 	X	 	
	 [***]
	  	 	X	  	 	X	 	X	 	X	 	X	 	X	 	X	 	X
	 [***]
	  				 	X	 	X	 	X	 	X	 	X	 	X	 	X
	 [***]8
	  	 	X	  	 	X	 		 	X	 	X	 	X	 	X	 	X
	 [***]
	  				 	X	 		 		 	X	 		 	X	 	
	 [***]
	  				 	X	 		 		 	X	 		 	X	 	X

  

	1 	[***] 


  

			
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	Protocol VB-201-079	  	VB-201

  

 Figure 1. STUDY DIAGRAM 
  





 

  

			
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	2.0	LIST OF ABBREVIATIONS 

  

			
	 Abbreviation/ Acronym
	  	 Definition

		
	AE	  	Adverse Event
		
	ALT	  	Alanine transaminase
		
	ANCOVA	  	Analysis of Covariance
		
	AST	  	Aspartate transaminase
		
	BSA	  	Body Surface Area
		
	BUN	  	Blood Urea Nitrogen
		
	CFR	  	Code of Federal Regulations
		
	CRA	  	Clinical Research Associate
		
	CRF	  	Case Report Form
		
	CRO	  	Contract Research Organization
		
	DLQI	  	Dermatology Life Quality Index
		
	DSM-LV-TR	  	Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
		
	ECG	  	Electrocardiogram
		
	eCRF	  	Electronic Case Report Form
		
	EDC	  	Electronic Data Capture
		
	ET	  	Early Termination
		
	FDA	  	Food and Drug Administration
		
	GCP	  	Good Clinical Practice
		
	GGT	  	Gamma Glutamyl Transferase
		
	Hb	  	Hemoglobin
		
	HIPAA	  	Health Insurance Portability and Accountability Act
		
	HIV	  	Human Immunodeficiency Virus
		
	ICH	  	International Conference on Harmonization
		
	IEC	  	Independent Ethics Committee
		
	IL	  	Interleukin
		
	IRB	  	Institutional Review Board
		
	IUD	  	Intrauterine Device
		
	IVRS / IWRS	  	Interactive Voice Response System/Interactive Web Response
		
	LOCF	  	Last Observation Carried Forward
		
	MCH	  	Mean Corpuscular Hemoglobin
		
	MCHC	  	Mean Corpuscular Hemoglobin Concentration
		
	MCV	  	Mean Corpuscular Volume


  

			
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	 Abbreviation/ Acronym
	  	 Definition

		
	MedDRA	  	Medical Dictionary for Regulatory Activities
		
	MITT	  	Modified Intent-To-Treat
		
	PASI	  	Psoriasis Area and Severity Index
		
	PBMC	  	Peripheral Blood Mononuclear Cells
		
	PGA	  	Physician Global Assessment
		
	PIF	  	Pregnancy Information Form
		
	PK	  	Pharmacokinetics
		
	PO	  	By Mouth
		
	QD	  	Once Daily
		
	RBC	  	Red Blood Cell
		
	SAE	  	Serious Adverse Event
		
	SUSAR	  	Suspected Unexpected Serious Adverse Reaction
		
	TNF-a	  	Tumor Necrosis Factor-a
		
	ULN	  	Upper Limit of Normal
		
	URI	  	Upper Respiratory Infection
		
	UTI	  	Urinary Tract Infection
		
	VAS	  	Visual Analogue Scale
		
	VBL	  	Vascular Biogenics Ltd.
		
	WBC	  	White Blood Cell
		
	WHO	  	World Health Organization


  

			
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	Protocol VB-201-079	  	VB-201

  


	3.0	INTRODUCTION 

  

	 	3.1	Psoriasis: Pathophysiology and Unmet Medical Need 

 Psoriasis is a life-long, immune-mediated
inflammatory skin disease of unknown etiology, affecting up to 3% of the general population, with rates varying among geographic areas and races.1 Over 80% of patients have chronic plaque
psoriasis, characterized by recurrent exacerbations and remissions of thickened, erythematous, scaly patches of skin that can occur anywhere on the body. 

Psoriatic symptoms can cause physical discomfort (pain and pruritus), and when combined with the psychological effects of the disease often interfere with
everyday activities and negatively impact a patient’s quality of life.2,3 While there are many available treatments, these agents each have limited efficacy and/or significant side effects.
Thus, there remains a significant unmet need for a therapy that will provide high continuous efficacy and improved safety profile. 
 It is currently
believed that environmental factors, including microorganisms, instigate a cascade of events which lead to psoriasis initiation. 4 Once encountered by microbial components, toll-like receptors
(TLR) expressed on keratinocytes and dermal dendritic cells mediate the secretion of pro-inflammatory cytokines such as IL-6, IL-1, IL-12 and IL-23.5,6 These cytokines induce the generation of Th1
and Th17 cells which promote psoriasis pathogenesis.7,8,9 
 Vascular Biogenics Ltd (VBL) has developed
a small molecule, VB-201 (formerly known as CI-201 as seen in some of the figures) a new class of compounds, oxidized phospholipid analogs (lecinoxoids). VB-201 was found to inhibit TLR signaling restricted to TLR2 and TLR4, an effect attributed to
its binding to TLR2 and CD14. Consequently, when activated using TLR4 and TLR2 agonists in the presence of VB-201, antigen presenting cells showed impaired production of the Th1 and Th17- polarizing cytokines IL-12(p40) and IL-6 respectively. 

Given the putative TLR complicity in psoriasis, VB-201 has the potential to be an orally active drug for treating psoriasis. 

The current study is designed to test safety, efficacy, and tolerability of an oral preparation of VB-201 in patients with chronic plaque psoriasis. 

 

	 	3.2	Name and description of the investigational product 

 [***] 

 

	 	3.3	Summary of findings from nonclinical studies relevant to the trial 

 [***]


  

			
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[***] 
 5) [***] 

[***] 

  

			
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	3.4	Summary of findings from clinical studies 

  

	3.4.1	VB-201 Phase I Studies 

 [***] 
  


	3.4.2	VB-201 Phase II studies 

 VB-201 was further used in two Phase II clinical trials: 

1. [***] 

  

			
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[***] 
 2. VB-201-030: [***] 

  

			
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 [***] 
  

	3.5	Rationale for Route of Administration, Pharmaceutical Form, Dosage, Dosage Regimen and Treatment Period 


[***] 
  

	3.6	Rationale for the PASI 50 Endpoint 

 [***] 

  

			
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[***] 
  

	3.7	Rationale for the Use of Placebo 

 [***] 

  

			
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[***] 
  

	4.0	OBJECTIVES 

  

	 	4.1	Safety Objective 

  

	 	•	 	To examine the safety and tolerability of up to 24 weeks’ treatment with VB-201 or placebo in patients with psoriasis. 

  

	 	4.2	Efficacy Objective 

  

	 	•	 	Stage 1: To examine the effect of treatment with two different doses of VB-201 compared to placebo (initial 16 weeks) on measures of disease activity in patients with psoriasis. 


 

	 	•	 	Stage 2: To examine the effect of treatment with two different doses of VB-201 compared to placebo (24 weeks) on measures of disease activity in patients with psoriasis. 


 

	 	4.3	Exploratory Biomarker 

  

	 	•	 	[***] 

  

	5.0	INVESTIGATIONAL PLAN 

  

	 	5.1	Study Design 

 [***] 
  

	 	5.2	Number of Patients 

 [***] 

  

			
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[***] 
 Table 2. Composition of the patient identification number 

 

									
	 	  	 Combined site number
	  	 
	 Letter
	  	 Country number
	  	 Site number
	  	 Patient number

	S	  	Germany	  	01	  	Site numbers will be assigned in an ascending order: 01, 02, 03, 04...	  	 Patient numbers will be assigned in an

ascending order: 01, 02, 03, 04,...

	  	Spain	  	02	  	  
	  	Israel	  	03	  	  
	  	Poland	  	04	  	  

 The 7-digit randomization number is a combination of the letter R (1 digit), the combined site number (4 digits),
consisting of the country number (2 digits) and the site number (2 digits) and the patient number (2 digits). The site number is identical to the site number of the patient identification number. Patient numbers of the randomization number will
start with 51 to ensure clear distinction from patient identification numbers. Example: R010151 is the site number 0101 and the patient number 51. Refer to Table 3 below. 

Table 3. Composition of the randomization number 
  

									
	 	  	 Combined site number
	  	 
	 Letter
	  	 Country number
	  	 Site number
	  	 Patient number

	R	  	Germany	  	01	  	 Site numbers will be assigned in an ascending order: 01, 02, 03, 04...
	  	Patient numbers will be assigned in an ascending order: 51, 52, 53, 54,...
	  	Spain	  	02	  	  
	  	Israel	  	03	  	  
	  	Poland	  	04	  	  


  

			
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	 	5.3	Subject Selection 

  

	5.3.1	Inclusion Criteria  

 [***] 

 

	5.3.2	Exclusion Criteria  

 Patients who meet ANY of the following criteria will be excluded from
participation in this study: 
 1. [***] 

  

			
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	 	•	[***] 

  

	12	[***] 


  

			
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	Protocol VB-201-079	  	VB-201

  

 [***] 
  

	5.4	Subject Screening and Randomization 

 [***] 

 

	5.5	Duration of Participation 

 [***] 

 

	5.6	Protocol Amendments 

 [***] 
  

	5.7	Withdrawal Criteria 

 [***] 

  

			
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	Protocol VB-201-079	  	VB-201

  

 [***] 
  

	5.8	Study/Study Site Termination 

 [***] 

 

	6.0	STUDY DRUG 

  

	6.1	Formulation, Packaging, and Labeling 

 [***] 

  

			
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	Protocol VB-201-079	  	VB-201

  

 [***] 
  

	 	6.2	Storage and Handling 

 The study drug should be stored on site at room temperature, in a secured location
with access limited to authorized personnel. All boxes of study drug, both used and unused, must be saved for a drug audit by the Sponsor clinical monitor or an assigned designee. Once dispensed to the study subjects the study drug should be stored
at room temperature. Subjects should be instructed on the proper storage methods and conditions. 
  

	 	6.3	Accountability 

 Study drug (VB-201 and placebo) will be supplied by the Sponsor. It is the
responsibility of the Principal Investigator to supervise accurate monitoring of the receipt, storage, dispensing, and accounting of all study drug according to accepted medical and pharmaceutical practice. 

Copies of all invoices of study drug shipments must be retained. Accurate, original site records of study drug inventory and dispensing must be maintained
using the forms provided. All shipment, accountability, and dispensing records must be made available for inspection by the Sponsor or the designated CRO upon request. 

Each site must keep all used and unused cartons in their original kit packaging until the Study Monitor either arranges return to the distribution center or
gives instruction on their disposal. If any unused cartons remain at the end of the study, they will be accounted for at the Site Close-Out Visit in the presence of the Study Monitor, who will provide instructions on their disposal. If the Study
Monitor directs the site to dispose of study drug or empty blister packs, disposal should be according to the institution standard operating procedures and all applicable local and national regulations. 

 

	6.4	Access to Blinded Treatment 

 A subject’s treatment assignment should only be unblinded when
knowledge of the treatment is essential for the further management of the subject. Unblinding for any other reason will be considered a protocol violation. 

  

			
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 The Principal Investigator should make every effort to contact either the CRO or the Sponsor before
unblinding any subject’s treatment assignment, but must do so within one working day after the event and must document the unblinding in the subject’s source documentation. 

The identity of the treatment group assigned to subjects can be provided, in an emergency only, by the centralized randomization system via the CRO. The
Principal Investigator or his/her designee is responsible for ensuring that the instructions on how to perform a code break are stored safely, that their location is known, and that access is readily available to the relevant staff in case of an
emergency. A separate Sponsor representative who is not involved with the study will also have access to unblinding information if required. 
 The
CRO’s safety officer will report SUSARs on the Sponsor’s behalf and will break the blind for SUSAR reporting. 
  

	6.5	Administration of Study Drug 

  

	6.5.1	Dosage 

 [***] 

Table 4. VB-201 Drug Distribution 

  

			
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	 Treatment Group
	  	 Carton AM
	  	 Carton PM

	[***]	  	[***]	  	[***]

 Subjects will be instructed to take 2 capsules from the morning blister (white) pack at breakfast time with food and
2 capsules from the evening blister (silver) pack at dinner time with food every day for up to 24 weeks. 
 Each carton will be labeled to meet
regional regulatory requirements. All capsules will be identical in appearance. There is no provision under this protocol for dose adjustments by the Investigator. 
  

	6.5.2	Assignment of Treatment Cartons 

 At each visit, the Investigator or designee will first assess the
subject to confirm eligibility to continue to receive study drug. After eligibility is confirmed, study medication with the appropriate subject number can be distributed to the subject [***] 

 

	6.5.3	Compliance 

 [***] 
  

	7.0	PRIOR AND CONCOMITANT MEDICATION 

 [***] 

  

			
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 [***] 
  

	8.0	OUTCOME MEASURES 

  

	 	8.1	Efficacy Assessments 

 [***] 

  

			
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 Table 5. Clinical Assessments Relating to Efficacy 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]


  

			
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 Table 5. Clinical Assessments Relating to Efficacy (cont.) 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]

 W-week, D-day, ET-early termination 

[***] 

  

			
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 Plaque Photography 

[***] 
  

	 	8.2	Safety Assessments 

  

	8.2.1	Physical Examination Assessments 

 The physical exam assessments relating to safety to be performed
during the study are described in Table 6. 
 Table 6. Physical Examination Assessments Relating to Safety 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]

 W-week, D-day, ET-early termination 
  

	8.2.2	Clinical Laboratory & Other Safety Assessments 

 The clinical laboratory and other tests
relating to safety to be performed during the study are described in Table 7. 

  

			
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 Table 7. Clinical Laboratory & Other Assessments Relating to Safety 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]

 W-week, D-day, ET-early termination 
  

	*	If values are abnormal at the Week 24/ET visit, they should be repeated at the Week 28 visit to ensure values have returned to within normal limits. 


 

	8.2.3	Population Pharmacokinetics 

 Blood collected for trough levels of VB-201 during the study are described
in Table 8: 

  

			
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 Table 8. Population Pharmacokinetics 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]

  

	8.2.3.1	Blood and Urine Samples 

 [***] 

 

	8.2.3.2	Risk Assessment 

 [***] 
  

	8.2.4	Study Withdrawals 

 [***] 
  

	8.2.5	Adverse Events and Serious Adverse Events 

 Adverse events and serious adverse events (SAEs) are
discussed in detail in Section 9. 
  

	 	8.3	Exploratory Assessments 

 The clinical laboratory and other tests relating to exploratory assessments to
be performed during the study are described in Table 9: 
 Table 9. Clinical Laboratory for Exploratory Assessments 

 

					
	 Assessment
	  	 Study Visit
	  	 Description

	[***]	  	[***]	  	[***]

 D- day, W-week, ET-early termination 

  

			
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	8.3.1	Inflammatory Related Biomarkers 

 [***] 

 

	9.0	SCHEDULE OF STUDY ASSESSMENTS 

 [***] 

 

	 	9.1	Screening Visit 

 [***] 
  

	 	9.2	Baseline 

 [***] 

  

			
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	 	•	 	[***] 

 NOTE: [***] 
  

	 	9.3	Week [***] 

 Each subject will be contacted by telephone at Week [***] and the following will be
performed: 

  

			
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	 	•	 	[***] 

  

	 	9.4	Week [***] 

 Each of the following assessments will be performed on Week, [***] 

 

	 	•	 	[***] 

  

	 	9.5	Week [***] 

 Each of the following assessments will be performed on Week [***]: 

 

	 	•	 	[***] 


  

			
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	 	•	 	[***] 

  

	 	9.6	Week [***] 

 Each of the following assessments will be performed on Week [***] 

 

	 	•	 	[***] 

  

	 	9.7	Week [***] 

 Each of the following assessments will be performed at Week [***] or, if a subject
discontinues early from the study: 
  

	 	•	 	[***] 


  

			
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	 	•	 	[***] 

  

	9.8	Week [***] 

 Patients who complete the Week [***] and those who discontinue early from the study will
return to the clinic on Week [***] after their last study medication dose if the subject discontinued early from the study, for a follow-up evaluation and the following assessments: 

 

	 	•	 	[***] 

  

	10.0	Adverse Events 

  

	 	10.1	Definition of Adverse Event 

 [***] 

  

			
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 [***] 

Severity Assessment 
 [***] 

Causality Assessment 
 [***] 

 

	10.2	Definition of Serious Adverse Event 

 [***] 

  

			
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	 	•	 	[***] 

  

	10.3	Reporting and Documentation 

 The Investigator must report all directly observed AEs and all
spontaneously reported AEs. At each visit the Investigator will ask the subject a nonspecific question (e.g., “Have you noticed anything different since your last visit?”) to assess whether any AEs have been experienced since the last
report or visit. AEs will be identified and documented on the AE page of the CRF in appropriate medical terminology. Details of the event must include severity, relationship to study drug, duration, action taken, and outcome. 

The action(s) taken regarding the AE are classified as follows: 

Treatment for event 
  

	 	•	 	None 

  

	 	•	 	Concomitant medication given or changed 

  

	 	•	 	Hospitalization 

  

	 	•	 	Others 

  

	 	•	 	Unknown (only applicable if patient has been lost to follow up). 

 Action taken with study medication

  

	 	•	 	None 


  

			
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	 	•	 	Temporary discontinuation 

  

	 	•	 	Permanent discontinuation 

  

	 	•	 	Unknown (only applicable if patient has been lost to follow up). 

 The outcome of the AE is classified as
follows 
  

	 	•	 	Recovered 

  

	 	•	 	Recovered with sequelae 

  

	 	•	 	Not recovered 

  

	 	•	 	Death 

  

	 	•	 	Unknown (only applicable if patient has been lost to follow up). 

 Furthermore it must be stated if the study
was discontinued permanently for patient (yes, no) due to the AE/ SAE 
 The Principal Investigator is responsible for evaluating all AEs, obtaining
supporting documents, and determining that documentation of the event is adequate. The Principal Investigator may delegate these duties to Sub-investigators and must assure that these Sub-investigators are qualified to perform these duties under the
supervision of the Principal Investigator. 
 In the event that a subject is withdrawn from the study because of an AE, it must be recorded on the CRF. The
subject should be followed and treated by the Investigator until the AE has resolved or a new chronic baseline has been established. 
 Any SAE, whether or
not considered related to the study drug, must be reported immediately (within 24 hours) upon learning of the event (See Study Manual). The Investigator or his designee should complete the study-specific SAE Report Form. Investigators should not
wait to collect additional information that fully documents the event before notifying VBL or its designee of an SAE. Contact numbers for reporting SAEs and events of concern will be provided prior to the start of the study. 

It is the responsibility of the Investigator to report SAEs to their IRB/IEC according to the standard operating procedures and policies of the IRB or EC. At
a minimum, events identified by the Sponsor to require expedited reporting as serious, unexpected, and possibly related to study drug must be brought to the attention of the responsible IRB/IEC. Adequate documentation must be provided to VBL or its
designee that the IRB or EC was properly notified. 
  

	10.4	Patient Stopping Rules 

 The following stopping rules will be utilized in this study: 

 

	 	1.	[***] 


  

			
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	 	2.	[***] 

 Subjects who permanently discontinue study medication shall return for an Early Termination visit and
subsequently for a final safety visit 4 weeks from the last dose. 
  

	10.5	Pregnancy 

 [***] 
  

	11.0	STATISTICAL CONSIDERATIONS 

  

	 	11.1	Statistical Methods 

  

	11.1.1	Comparisons of Interest 

 [***] 

 

	11.1.2	Sample Size Determination 

 [***] 

 

	11.1.3	Subject Population/Data Sets To Be Evaluated 

  

	11.1.3.1	  Modified Intent-To-Treat (MITT) Population 

 [***] 

  

			
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 [***] 
  

	11.1.3.2	Per-Protocol Population 

 [***] 

 

	11.1.3.3	Safety Population 

 [***] 
  

	11.1.4	Randomization 

 [***] 
  

	11.2	Statistical Analyses 

 [***] 
  


  

			
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	11.2.1	Subject Disposition 

 [***] 
  

	11.2.2	Demography 

 [***] 
  

	11.2.3	Efficacy Analysis 

 [***] 
  

	11.2.3.1	Primary Efficacy Endpoints 

  

	11.2.3.1.1	Stage 1 Primary Efficacy Endpoints 

 [***] 

 

	11.2.3.1.2	Stage 2 Primary Efficacy Endpoints 

 [***] 

  

			
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	11.2.3.2	Secondary Efficacy Endpoints 

  

	11.2.3.2.1	 Stage 1 Secondary Efficacy Endpoints 

 [***] 

 

	11.2.3.2.2	 Stage 2 Secondary Efficacy Endpoints 

 [***] 

  

			
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	 	3.	[***] 

  

	11.2.3.3	Tertiary Endpoints 

  

	11.2.3.3.1	 Stage 1 Tertiary Endpoints 

 [***] 

 

	 	4.	[***] 

  

	11.2.3.3.2	 Stage 2 Tertiary Endpoints 

 [***] 

  

			
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 [***] 
  

	11.2.4	Safety Analysis 

 [***] 
  

	11.2.4.1	Adverse Events 

 [***] 
  

	11.2.4.2	Laboratory Parameters 

 [***] 

  

			
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	11.2.4.3	Vital Signs 

 [***] 
  

	11.2.4.4	Withdrawals 

 [***] 

11.2.4.5 Deaths 
 All deaths will be listed. 

 

	11.2.4.6	Dropouts 

 Dropout rates due to rescue intervention in each of the VB-201 groups will be compared to the
placebo group using Fisher’s exact test. 
  

	11.2.5	Concomitant Medications 

 [***] 

 

	12.0	DATA RECORDING, MONITORING, AND RETENTION 

  

	 	12.1	Source Documents 

 Source records are original documents, data, and records (e.g., medical records, raw
data collection forms, pharmacy dispensing records, recorded data from automated instruments, laboratory data) that are relevant to the clinical trial. The Investigator will prepare and maintain adequate and accurate source documents. These
documents are designed to record all observations and other pertinent data for each subject enrolled in this clinical trial. Source records must be adequate to reconstruct all data transcribed onto the Case Report Forms (CRFs). 

 

	12.2	Case Report Forms (CRFs) 

 All data will be recorded on electronic data capture (EDC) system CRFs
provided by the Sponsor or its designee. All electronic case report forms (eCRFs) should be completed by designated study personnel in a timely fashion. 

All missing data must be explained in the subject’s source record. All eCRFs must be reviewed and verified by the investigator for accuracy,
completeness, legibility, and timeliness of reporting to the Sponsor. 
  

	12.3	Record Retention 

 Investigators are required to maintain all study documentation, informed consent forms
and subject information sheets and adequate records for the receipt and disposition of all study drugs in a secure and safe facility. 

  

			
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 Essential documents must be retained for at least 2 years following the FDA or other regulatory approval date
of the drug, or until two years after the drug investigational program is discontinued unless a longer period is required by applicable law or regulation. Only the Sponsor can notify an Investigator when any records may be discarded. If the
investigator wishes to assign responsibility for the study records to another party or have them moved to another location, the Sponsor must be notified in advance. When the study documents no longer need to be retained, it is the responsibility of
the Sponsor to inform the investigator/institution. Subject identity information will be maintained for 15 years unless a longer period is required by applicable law or regulation. 

 

	12.4	Monitoring Requirements 

 Following pre-qualification and initiation of the study site, periodic
monitoring visits will be made by the Sponsor or its designated representative. The investigator must provide sufficient space and allocate sufficient time for the monitor to inspect subject source records, case report forms, drug accountability
records, and regulatory documents. 
 The study monitor is responsible for visiting the study site at regular intervals to verify the following: 

 

	 	•	 	The rights and well-being of human Patients are protected; 

  

	 	•	 	The reported data are accurate, complete, and verifiable from source documents; 

  

	 	•	 	The conduct of the trial is in compliance with the currently approved protocol, amendment(s), International Conference on Harmonisation (ICH) Good Clinical Practices (GCP), U.S. Food and Drug Administration (FDA) Code
of Federal Regulations (CFR), and any other applicable national and local regulatory requirements. 

 The study monitor should have access to
subject medical records and other study-related records needed to verify the entries in the database. 
 The Investigator must make study data accessible to
the study monitor, the Sponsor, authorized representatives of the Sponsor (e.g., CRO), and Regulatory Agencies/Competent Authorities upon request. 
  

	12.5	Subject Confidentiality 

 The Investigator must ensure that the subject’s anonymity is maintained.
On the CRFs or other documents submitted to the Sponsor and/or designated CRO, Patients should be identified by a Subject Identification number and/or randomization number. 

Documents that are not for submission to the Sponsor and/or designated CRO (e.g., signed informed consent forms and subject information sheets) should be kept
in strict confidence by the Investigator in compliance with Federal regulations/ICH GCP Guidelines. It is required that the Investigator and institution permit authorized representatives of the company, of the regulatory agency, and the IRB/IEC
direct access to review the subject’s original medical records for verification of study-related procedures and data. 
 Direct access includes
examining, analyzing, verifying, and reproducing any records and reports that are important to the evaluation of the study. The Investigator is obligated to inform the subject that his/her study-related records will be reviewed by the above named


  

			
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 representatives, although the confidentiality of his/her records will be maintained as much as reasonably
possible. 
 For the purposes of the study, only the data set forth in this protocol (including the CRFs) will be obtained regarding participating Patients
(whether screen failures or enrolled Patients). Such data shall: 
  

	 	•	 	be processed in accordance with this Protocol or as otherwise instructed by the Sponsor; 

  

	 	•	 	be processed solely for the purposes of the study and in the manner specified in this Protocol; 

  

	 	•	 	not be processed in any manner incompatible with the purposes of the study; 

  

	 	•	 	be accurate, up to date and corrected to address any inaccuracies or omissions; 

  

	 	•	 	be maintained (as specified in this Protocol/using reasonable measures) to protect against accidental or unlawful destruction, accidental loss or damage, alteration, unauthorized disclosure or access and against other
unauthorized or unlawful forms of processing; 

  

	 	•	 	not be disclosed to any third party without the Sponsor’s prior written consent; and 

  

	 	•	 	be maintained as detailed in Section 12.3 unless a longer period is required by applicable laws or regulations. 


Any reasonably requested assistance shall be provided to assist the Sponsor to enable it to comply with any data-related notification obligations under
applicable laws or regulations. In the US, conduct of this study will comply with all provisions of HIPAA. The Sponsor shall be promptly informed of any communication received from a study subject regarding the data collected about him/her in
connection with the study. 
  

	13.0	ETHICS 

  

	 	13.1	Ethical Conduct of the Study 

 The study will be conducted in accordance with applicable national and
international laws and regulations, the ICH-GCP guideline and the ethics principles that have their origins in the Declaration of Helsinki. The protocol and the proposed informed consent form have to been reviewed and approved by a properly
constituted Independent Ethics Committee (IEC/IRB) before study start at a particular study site. Prior to study start, the principal investigator is required to sign the protocol signature page (page 3 of this study protocol) confirming his
agreement to conduct the study in accordance with these documents and all of the instructions and procedures found in this protocol and to give access to all relevant data and records to monitors, auditors, IRBs/IECs, and regulatory authorities as
required. 
  

	13.2	Local Regulatory Approval 

 The Sponsor or the CRO will supply the Competent Authorities of each
participating country with a dossier containing the required pharmacological, toxicological and pharmaceutical data on the compound, so as to obtain import and study approval. The study will not start in that country until this has been obtained
where appropriate. 

  

			
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	13.3	Ethics Committee Approval 

 The Principal Investigator at each site is responsible for obtaining
Institutional Review Board (IRB) or Independent Ethics Committee (IEC), approval for the protocol, informed consent form/ information sheet, and any advertisements to recruit Patients before being implemented at the investigative site. Written
approval of these documents must be obtained from the committee before any subject is enrolled at a center. 
 The Principal Investigator is also
responsible for the following interactions with the IRB/IEC: 
  

	 	•	 	Obtaining IRB/IEC approval for any protocol amendments and informed consent form revisions before implementing the changes; 

  

	 	•	 	Providing the IRB/IEC with any required information before or during the study; 

  

	 	•	 	Submitting progress reports to the IRB/IEC, as required, during the conduct of the study; requesting re-review and approval of the study, as needed; providing copies of all IRB/IEC re-approvals and relevant
communication to the CRO or the Sponsor; 

  

	 	•	 	Notifying the IRB/IEC of all serious and unexpected AEs related to the study drug reported by the Sponsor or the CRO, as required. Documentation of this notification should be retained. 


 

	13.4	Subject Information and Informed Consent 

 No investigator may involve a human being as a subject in
research unless the Investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. An Investigator shall seek such consent only under circumstances that provide the
prospective subject or the subject’s legally authorized representative sufficient opportunity to consider whether or not to participate, and that minimize the possibility of coercion or undue influence. The information that is given to the
subject or the representative shall be in a language understandable to the subject or representative. 
 The Sponsor or its designated representative will
provide the Investigator with a sample consent form. Local and/or institutional requirements may require disclosure of additional information in the informed consent. Any changes to the consent form must be submitted to the sponsor or its designated
representative for approval prior to submission to the IRB/IEC. The IRB/IEC must review the consent form for approval/favorable opinion, and a copy of the approved consent form must be submitted to the Sponsor or its designated representative prior
to initiation of the study. 
 Before implementing any study procedure, informed consent shall be documented by the use of an IRB/IEC approved written
consent form signed and dated by the subject or the subject’s legally authorized representative at the time of consent. A copy of the signed informed consent will be given to the subject or the subject’s legally authorized representative.
The original signed consent must be maintained by the Investigator and available for inspection by the Sponsor, its designated representative, or regulatory authority at any time. 

  

			
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	14.0	PUBLICATION 

 The Sponsor recognizes the importance of communicating clinical study data and therefore it
is the intent of the Sponsor to publish the results of this trial, the details of which will be provided in the Clinical Study Agreement. 
  

	15.0	LIST OF APPENDICES 

 Appendix A: ELEMENTS OF THE PSORIASIS AREA AND SEVERITY INDEX (PASI) 

  

			
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 Appendix A: ELEMENTS OF THE PSORIASIS AREA AND SEVERITY INDEX (PASI) 

 

			
	 	  	  


  

									
	 	  	 Head
	  	 Upper Extremities
	  	 Trunk
	  	 Lower extremities

	[***]	  		  		  		  	
					
	[***]	  		  		  		  	
					
	[***]	  		  		  		  	
					
	[***]	  		  		  		  	
					
	[***]	  		  		  		  	
					
	[***]	  		  		  		  	
					
	[***]	  	[***]	  	[***]	  	[***]	  	[***]
					
	[***]	  		  		  		  	

 [***] 

  

			
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	Protocol VB-201-079	  	VB-201

  


	16.0	REFERENCES 

  

	1.	Krueger GG, Duvic M. Epidemiology of psoriasis: clinical issues. J Invest Dermatol. 1994;102(6):14S-8S. 

  

	2.	Kimball AB, Jacobson C, Weiss S, et al. The psychosocial burden of psoriasis. Am J Clin Dermatol. 2005;6(6):383-92. 

  

	3.	Russo PA, Ilchef R, Cooper AJ. Psychiatric morbidity in psoriasis: a review. Australas J Dermatol. 2004;45(3):155-9. 

  

	4.	Nestle FO, Kaplan DH, Barker J. Mechanisms of Disease: Psoriasis. N Engl J Med 2009 Jul;361:496-509. 

  

	5.	Nestle FO, Di Meglio P, Qin JZ. Skin immune sentinels in health and disease. Nature Reviews Immunology 2009 
Oct;9:679-690. 

  

	6.	Di Meglio P, Perera GK, Nestle FO. The Multitasking Organ: Recent Insights into Skin Immune Function. Immunity 2011 Dec;35: 857-869. 


 

	7.	Austin LM, Ozawa M, Kikuchi T, et al. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1
(cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol. 1999 Nov;113(5):752-9. 


 

	8.	Schlaak JF, Buslau M, Jochum W, et al. T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol. 1994 Feb;102(2):145-9. 


 

	9.	Fitch E, Harper E, Skorcheva I, et al. A. Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep. 2007 Dec;9(6):461- 7. 


 

	10.	Vascular Biogenics Ltd. VB-201 Investigator’s Brochure Version 13. Internal archive; 2012. 


  

			
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	Protocol VB-201-079	  	VB-201

  

 CLINICAL PROTOCOL 

 

					
		 	Title:	  	A Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Oral VB-201 in Patients with Moderate to Severe Plaque Psoriasis
			
		 	Protocol No.	  	VB-201-079
			
		 	Eudra CT No.:	  	2012-002763-10
			
		 	Investigational Product:	  	VB-201
			
		 	Indication:	  	Plaque Psoriasis
			
		 	Development Phase:	  	2
			
		 	Sponsor:	  	Vascular Biogenics Ltd.
		 		  	6 Jonathan Netanyahu St.
		 		  	Or Yehuda, Israel 60376
		 		  	Phone: 972-3-6346450
		 		  	Fax: 972-3-6346449
			
		 	Version:	  	2.2 (Poland and Israel only)
			
		 	Date:	  	December 2, 2013

 CONFIDENTIAL 

This document contains proprietary and confidential information of VBL. Acceptance of this document constitutes agreement by the recipient that no previously
unpublished information contained herein will be published or disclosed without the prior written approval of Vascular Biogenics Limited with the exception that this document may be disclosed to study personnel under your supervision who need to
know the contents for conducting the study and appropriate Institutional Review Boards (IRBs)ZEthics Committees (1EC) under the condition that the personnel have agreed to keep this information confidential. The foregoing shall not apply to
disclosure required by governmental regulations or laws, however, VBL shall be promptly notified of any such disclosure. 

  

			
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 Attachment No. 4 

List of SOPs applicable for the Study conduct 

KCR SOP AND ASSOCIATED FORMS AND TEMPLATES 
  

							
	 	  	Version	  	Effective date	 
	 101.1 MED. Feasibility process
	  	5	  	 	06 Dec 11	  
			
	 Associated Forms And Templates:

101.1 MED. 01 Short Feasibility Worksheet
	  	2	  	 	08 Mar 10	  
	 101.1 MED. 02 Feasibility Questionnaire
	  	3	  	 	06 Dec 11	  
	 101.1 MED. 03 Feasibility Results
	  	2	  	 	08 Mar 10	  
	 101.1 MED. 04 Thank You Letter
	  	1	  	 	06 Dec 11	  
			
	 102.1 MED. Regulatory Submission for Clinical Study Application
	  	4	  	 	13 Dec 12	  
			
	 102.3 MED. Updating Clinical Study Documentation
	  	2	  	 	13 Aug 12	  
			
	 102.5 MED. Management of Regulatory Process
	  	2	  	 	13 Aug 12	  
			
	 103.1 MED. Pre-Study Visit
	  	2	  	 	21 Feb 11	  
			
	 Associated Forms And Templates:
	  		  			
	 103.1 MED. 01 Confirmation Pre-study Letter
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 02 Pre-study Visit Checklist
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 03 Pre-study Visit Report
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 04 Follow-up Pre-study Visit Letter
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 05 Site Selection Summary
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 06 Site Selection letter
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 07 Site Exclusion Letter
	  	2	  	 	21 Feb 11	  
	 103.1 MED. 08 Declaration on Facilities

103.1 MED. 09 Curriculum Vitae form

103.1 MED. 10 Contact Data Form

103.1 MED. 11 Pre-study Visit Agenda
	  	2
 3

2
 1
	  	 
  

 
  
	21 Feb 11
 21 Jun 11

21 Feb 11
 21 Feb
11
	  
   

  
   

			
	 104.1 MED. Informed Consent Form
	  	3	  	 	10 Nov 11	  
			
	 Associated Forms And Templates:
	  		  			
	 104.1 MED. 01 Informed Consent Form Approval Process
	  	2	  	 	10 Nov 11	  
	 104.1 MED. 02 Informed Consent Form Checklist
	  	2	  	 	10 Nov 11	  
	 104.1 MED. 03 Patient Information and Informed Consent Form Version Log
	  	2	  	 	10 Nov 11	  
	 104.1 MED. 04 Informed Consent Form local adjustment
	  	3	  	 	10 Nov 11	  


  

			
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	 105.1 MED. Initiation Visit
	  	2	  	 	04 Mar 11	  
			
	 Associated Forms And Templates:
	  		  			
	 105.1 MED. 01 Confirmation Initiation Visit Letter
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 02 Site Initiation Visit Checklist
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 03 IMP Release Form
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 04 Site Green Light Approval
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 05 Site Initiation Visit Report
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 06 Delegation of Responsibilities Log
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 07 Site Visit Log
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 08 Subject Identification Log
	  	3	  	 	04 Mar 11	  
	 105.1 MED. 09 Subject Screening and Randomization Log
	  	3	  	 	04 Mar 11	  
	 105.1 MED. 10 Follow-up Site Initiation Visit Letter
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 11 Financial Disclosure Form
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 12 Subject pre-screening Log
	  	2	  	 	04 Mar 11	  
	 105.1 MED. 13 Site Initiation Visit Agenda
	  	2	  	 	22 Jan 13	  
	 105.1 MED. 14 List of Site Initiation Visit Activities
	  	1	  	 	04 Mar 11	  
	 105.1 MED. 15 Consent to Processing Personal Data
	  	1	  	 	02 Jun 11	  
	 105.1 MED. 16 Instruction on How to Manage Consent for Personal Data in Clinical Operation Department
	  	1	  	 	27 Aug 12	  
			
	 106.1 MED. Monitoring Visit
	  	2	  	 	18 Apr 11	  
			
	 Associated Forms And Templates:
	  		  			
	 106.1 MED. 01 Confirmation Monitoring Visit Letter
	  	2	  	 	18 Apr 11	  
	 106.1 MED. 02 Monitoring Visit Report
	  	3	  	 	18 Apr 11	  
	 106.1 MED. 03 Contact Report
	  	2	  	 	18 Apr 11	  
	 106.1 MED. 04 Subject Visit Status
	  	2	  	 	18 Apr 11	  
	 106.1 MED. 05 Note to File
	  	3	  	 	18 Apr 11	  
	 106.1 MED. 06 Follow-up Monitoring Visit Letter
	  	2	  	 	18 Apr 11	  
	 106.1 MED. 07 Monitoring Visit and Reporting Plan
	  	2	  	 	18 Apr 11	  
	 106.1 MED. 08 Data Clarification Form

106.1 MED. 09 Site Personal Training Log

106.1 MED. 10 Confidentiality Violation Log
	  	1
 1

1
	  	 
  

 
	18 Jul 11
 26 Jun 12

26 Jun 12
	  
   

  

			
	 106.2 MED. Taking Over The Study
	  	3	  	 	31 May 13	  
			
	 Associated Forms And Templates:
	  		  			
	 106.2 MED. 01 CRA Site Take-Over Checklist
	  	5	  	 	31 May 13	  
	 106.2 MED. 02 CTA Take-Over Checklist
	  	2	  	 	31 May 13	  
			
	 106.3 MED. Co-Monitoring Visit
	  	2	  	 	25 Jul 11	  
			
	 106.3 MED. 02 Co-monitoring Visit Report: Quality Control Assessment
	  	2	  	 	25 Jul 11	  
			
	 106.4 MED. Reporting Protocol Deviations
	  	2	  	 	10 Aug 10	  
			
	 Associated Forms And Templates:
	  		  			
	 106.4 MED. 01 Protocol deviation report

106.4 MED. 02 Protocol Deviation Cumulative List
	  	2
 1
	  	 
  
	10 Aug 10
 10 Aug 10
	  
   

			
	 107.1 MED. Close-out Visit
	  	3	  	 	29 Dec 11	  


  

			
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 Associated Forms And
Templates:
	  		  			
	 107.1 MED. 01 Confirmation Close-out Visit Letter
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 02 Close out Visits Plan
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 03 Close out Visit Checklist
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 04 Close out Visit Report
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 05 Record Retention Form
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 06 Site Close out Assessment
	  	2	  	 	30 Apr 11	  
	 107.1 MED. 07 Follow-up Close out Visit Letter
	  	2	  	 	30 Apr 11	  
			
	 108.1 MED. Translation

 
 Associated Forms And Templates:

108.1 MED. 01 Translation Certificate
	  	3
 3
	  	 
  
	19 Sep 11
 19 Sep 11
	  
   

			
	 109.1 MED. Clinial Trial Documents
	  	4	  	 	16 Sep 13	  
			
	 Associated Forms And Templates:
	  		  			
	 109.1 MED 01 Essential Documents
	  	4	  	 	16 Sep 13	  
			
	 109.3 MED. Trial Master File
	  	1	  	 	16 Sep 13	  
			
	 Associated Forms And Templates:
	  		  			
	 109.2 MED. 01 Trial Maser File Table of Content
	  	1	  	 	16 Sep 13	  
	 109.2 MED. 02 Trial Maser File and Shadow File Review Form

109.2 MED. 03 TMF Transfer Form

109 3 MED 04 Study Documentation Management Form
	  	1
 1

1
	  	 
  

 
	16 Sep 13
 16 Sep 13

16 Sep 13
	  
   

  

			
	 109.5 MED. Investigator’s File
	  	1	  	 	16 Sep 13	  
			
	 Associated Forms And Templates:
	  		  			
	 109.5 MED. 01 Investigator’s File Table of Content
	  	1	  	 	16 Sep 13	  
			
	 109.5 MED. Electronic Study Folder and Shadow File

 
 109.7 MED.01 Shadow File Coordinators Log

109.7 MED.02 Electronic Folder Names

109.7 MED.03 Example of Electronic Study Folder and Shadow File Structure
	  	1
 1

1
 1
	  	 
  

 
  
	16 Sep 13
 16 Sep 13

16 Sep 13
 16 Sep
13
	  
   

  
   

			
	 110.1 MED. Clinical Supplies
	  	3	  	 	16 Sep 13	  
			
	 Associated Forms And Templates:
	  		  			
	 110.1 MED. 01 Temperature Log
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 02 Clinical Supply Shipment Management Log
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 03 Clinical Supply Accountability Form
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 04 Re-labelling Report
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 05 Investigational product RECALL form
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 06 Investigational product RETURN form
	  	3	  	 	16 Sep 13	  
	 110.1 MED. 07 Clinical Supply Destruction Report

110.1 MED.08 Site Investigational Product Accountability Log
	  	3
 1
	  	 
  
	16 Sep 13
 16 Sep 13
	  
   

			
	 111.1 MED. Clinical Trial Materials
	  	2	  	 	30 Sep 13	  
			
	 Associated Forms And Templates:
	  		  			
	 111.1 MED.01 Trial Supply Shipment Form
	  	4	  	 	30 Sep 13	  
	 111.1 MED.02 Controlled Copy Distribution Log
	  	3	  	 	30 Sep 13	  
	 111.1 MED.03 Frozen Samples storage log
	  	3	  	 	30 Sep 13	  
	 111.1 MED.04 Investigator’s Brochure Acknowledgement of Receipt
	  	2	  	 	30 Sep 13	  


  

			
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	 112.1 MED. Serious Adverse Event Reporting
	  	 	3	  	  	 	08 Mar 13	  
			
	 Associated Forms And Templates:
	  				  			
	 112.1 MED. 01 SAE Pregnancy Report Form
	  	 	3	  	  	 	08 Mar 13	  
			
	 112.2 MED. Distribution of SUSAR reports
	  	 	2	  	  	 	15 Sep 11	  
			
	 Associated Forms And Templates:
	  				  			
	 112.2 MED. 01 SUSAR Reports Tracking Log
	  	 	2	  	  	 	15 Sep 11	  
			
	 112.5 MED. Safety Management Principles
	  	 	1	  	  	 	16 Sep 2013	  
			
	 114.1 MED. Insurance in Clinical Trial

 
 Associated Forms And Templates:

114.1 MED. 01 Questionnaire for Insurance Purposes
	  	 
  
	3
 3
	  
   
	  	 
  
	15 Apr 13
 15 Apr 13
	  
   

			
	 116.1 MED. Clinical Study Report
	  	 	3	  	  	 	28 Jun 13	  
			
	 Associated Forms And Templates:
	  				  			
	 116.1MED. 01 Clinical Study Report Tracking Log
	  	 	3	  	  	 	28 Jun 13	  
			
	 117.1 MED. Archiving Study Files
	  	 	3	  	  	 	09 Sep 13	  
			
	 Associated Forms And Templates:
	  				  			
	 117.1 MED. 01 Archiving Facility Log
	  	 	3	  	  	 	09 Sep 13	  
	 117.1 MED. 02 Archiving Coordinator Log
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 03 Archiving Coordinator Backup Log
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 04 Archiving Coordinator Take Over
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 05 Post Study Checklist
	  	 	3	  	  	 	09 Sep 13	  
	 117.1 MED. 06 Content of Archived Box
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 07 List of Archived Studies
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 08 Retrieve from Archives Request
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 09 Confirmation of Destruction
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 10 Inventory of Archiving Boxes
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 11 Inventory of Archiving Locking Seals
	  	 	2	  	  	 	09 Sep 13	  
	 117.1 MED. 12 Content of Archiving File
	  	 	2	  	  	 	09 Sep 13	  
			
	 117.3 MED Management of Electronic Correspondence
	  	 	1	  	  	 	29 Mar 13	  
			
	 121.1 MED. Contracts with Investigators and Investigational Sites
	  	 	4	  	  	 	01 Feb 10	  
			
	 Associated Forms And Templates:

121.1 MED. 01 Bilateral contract (investigator)

121.1 MED. 02 Bilateral contract (centre)
	  	 
  
	4
 4
	  
   
	  	 
  
	08 Aug 11
 08 Aug 11
	  
   

	 121.1 MED. 03 Tripartite contract (investigator & centre)

121.1 MED. 04 Bilateral contract (investigator-coordinator)

121.1 MED. 06 Lend agreement (investigator)

121.1 MED. 07 Lend agreement (centre)

121.1 MED. 08 Service agreement (contractor with team)
	  	 
  

 
  

 
	4
 4

2
 2

2
	  
   

  
   

  
	  	 
  

 
  

 
	08 Aug 11
 08 Aug 11

08 Aug 11
 08
Aug 11
 08 Aug 11
	  
   

  
   

  

	 121.1 MED. 09 Service agreement (single contractor)

121.1 MED. 10 Bilateral contract (investigator) – MD

121.1 MED. 11 Bilateral contract (centre) – MD
	  	 
  

 
	2
 2

2
	  
   

  
	  	 
  

 
	08 Aug 11
 08 Aug 11

08 Aug 11
	  
   

  

	 121.1 MED. 12Tripartite contract (investigator & centre) – MD
	  	 	2	  	  	 	08 Aug 11	  


  

			
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	 121.1 MED. 13 Bilateral contract (investigator-coordinator) – MD
	  	 	2	  	  	 	08 Aug 11	  
			
	 122.1 MED. Confidentiality Agreements and Confidentiality Obligation
	  	 	3	  	  	 	14 Mar 11	  
			
	 Associated Forms And Templates:

122.1 MED. 01 CA general unilateral (investigator—centre)

122.1 MED. 02 CA study specific unilateral (investigator—centre)

122.1 MED. 03 CA general unilateral (sponsor—contractor—other)

122.1 MED. 04 CA study specific unilateral (sponsor—contractor—other)

122.1 MED. 05 CA general mutual (sponsor—contractor—other)

122.1 MED. 06 CO in feasibility only (investigator)

122.1 MED. 07 CA/CO explanatory notice
	  	 
  

 
  

 
  

 
	2
 2

2
 2

2
 3

2
	  
   

  
   

  
   

  
	  	 
  

 
  

 
  

 
	15 Feb 11
 15 Feb 11

15 Feb 11

15 Feb 11

15 Feb 11

15 Feb 11

01 Mar 11
	  
   

  
   

  
   

  

			
	 123.1 MED. Principles of drawing contracts and master service agreements
	  	 	2	  	  	 	28 Mar 11	  
			
	 Associated Forms And Templates:

123.1 MED. 01 KCR Group Contract Template:

        Master Service Agreement

123.1 MED. 02 KCR Group Contract Template:

        Service Agreement for a clinical study conduct
	  	 
  
	2
 1
	  
   
	  	 
  
	28 Mar 11
 20 Oct 08
	  
   

			
	 124.1 MED. Fraud and Misconduct
	  	 	3	  	  	 	11 Feb 13	  
			
	 125.1 MED. Purchases Within a Project
	  	 	1	  	  	 	25 Jul 11	  
			
	 127.1 MED. Legislation in Clinical Trials
	  	 	2	  	  	 	31 Jul 13	  
			
	 127.3 MED Regulatory Intelligence

 
 Associated Forms And Templates:

127.3 MED.01 Regulatory Intelligence Responsibilities
	  	 
  
	1
 1
	  
   
	  	 
  
	28 Dec 12
 28 Dec 12
	  
   

			
	 128.1 MED. Communication with Subcontractor

 
 Associated Forms And Templates:

128.1 MED. 01 Subcontractor Tracking Log
	  	   
  
	1  
 1
	    
   
	  	   
  
	01 Sep 11  

01 Sep 11
	    
   

			
	 129.1 MED. Annual Progress Report to Competent Authorities
	  	 	2	  	  	 	30 Sep 11	  
			
	 Associated Forms And Templates:
	  				  			
	 129.1 MED. 01 Annual Progress Report Template
	  	 	2	  	  	 	30 Sep 11	  
			
	 130.1 MED. Preparing Monitoring Plan
	  	 	1	  	  	 	25 Nov 11	  
			
	 Associated Forms And Templates:
	  				  			
	 130.1 MED. 01 Monitoring Plan
	  	 	1	  	  	 	25 Nov 11	  
			
	 131.1 MED. Communication Plan

 
 Associated Forms And Templates:
	  	 	1	  	  	 	30 Apr 12	  
	 131.1 MED. 01 Communication GLOBAL Contact List
	  	 	1	  	  	 	30 Apr 12	  
	 131.1 MED. 02 Communication COUNTRY Contact List
	  	 	1	  	  	 	30 Apr 12	  
	 131.1 MED. 03 Communication VENDOR Contact List
	  	 	1	  	  	 	30 Apr 12	  
	 131.1 MED. 04 Study Team Delegation Log
	  	 	1	  	  	 	30 Apr 12	  


  

			
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	 131.1 MED 05 Communication Plan
	  	1	  	 	30 Apr 12	  
			
	 132.1 MED. Unbliding
	  	1	  	 	28 Aug 12	  
			
	 Associated Forms And Templates:
	  		  			
	 132.1 MED. 01 Unblinding Contact List
	  	1	  	 	28 Aug 12	  
	 132.1 MED. 02 Unblinding Report
	  	1	  	 	28 Aug 12	  
	 132.2 MED. 03 Unblinding Listing
	  	1	  	 	28 Aug 12	  
			
	 134.1.MED Principal Investigator Change

 
	  	1	  	 	04 Apr 13	  
	 Associated Forms And Templates:
	  		  			
	 134 1 MED 01 Principal Investigator Change Checklist 131.1. MED. 03 134

1 MED 02 Letter to Competent Authorities About Principal Investigator Change
	  	1
 1
	  	 
  
	04 Apr 13
 04 Apr 13
	  
   



  

			
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 Attachment No. 5 

List of third parties engaged by the Sponsor for the conduct of the Study 

 

	 	a.	Legal representative (SCIderm GmbH): CRO shall undertake the following obligation, and shall indemnify the sponsor for any damage in case it will breach such obligation: notify immediately SCIderm GmbH and the Sponsor
of any untoward occurrences, including serious breaches of the protocol, GCP or regulations, occurring in the clinical trial. 

  

	 	b.	Data Management: CRO shall act according to the procedures, as shall be determined for this clinical trial. 


  

			
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 Attachment No. 6 

Study Budget 

Specification of anticipated costs and expenses 
  

																					
	 Ref.
#
	  	 Service
	  	Job
position	 	  	Unit
Cost
(€)	 	  	Quantity
of hours
units	 	  	Total	 	  	 KCR Notes / Comments

	A	  	MEDICAL WRITING	  				  				  				  	 	[***]	  	  	[***]
							
	B	  	STUDY FAMILIARIZATION & TRAINING	  				  				  				  	 	[***]	  	  	
							
	B.1	  	Kick-off Meeting—attendance	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.3	  	Monitors training (therapeutic)	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.4	  	Monitors training (therapeutic)	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.5	  	Investigator’s meeting—attendance and travel	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.6	  	Investigator’s meeting—attendance and travel	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.11	  	Investigator’s meeting—attendance and travel	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.12	  	Investigator’s meeting—prepare presentation	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.13	  	Investigator’s meeting organization	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	B.14	  	Familiarization with study documentation, SOPs and study specifics	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	C	  	SITE MANAGEMENT IN HOUSE (including site payments)	  				  				  				  	 	[***]	  	  	
							
	C.1	  	Site contacts over phone and written communication	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	C.2	  	CRF off site management	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	C.3	  	Resolve issues & queries	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	C.4	  	Administer investigators grants	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]


  

			
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		  		  				  				  				  				  	[***]
							
	C.5	  	Collect Pre-Study/Regulatory Documentation from sites and Sponsor	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	D	  	STUDY ADMINISTRATION & DOCUMENT MANAGEMENT	  				  				  				  	 	[***]	  	  	
							
	D.1	  	Set up study Trial Master Files	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	D.2	  	Create Investigator Binders	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	D.3	  	Maintain & update study Trial Master Files and project specific files	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	D.4	  	Archive, retain or return Study Documentation	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E	  	STUDY AUTHORIZATION & CONTRACTS	  				  				  				  	 	[***]	  	  	
							
	E.1	  	Develop local Informed Consent Form	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.2	  	Develop local Informed Consent Form	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.3	  	Coordinate translation/preparation process (protocol synopsis, drug labels, back translation)	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.4	  	Translation and country adaptation of drug labels	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.5	  	Development of project specific contract template	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.6	  	Preparing countries specific contract templates from the project specific template	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.7	  	Negotiate Investigator Budget & CSA (+ 2nd for hospital authorities)	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.8	  	Negotiate Investigator Budget & CSA (+ 2nd for hospital authorities)	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.9	  	Development of Authorization Letters	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.10	  	Initial submission to CA and EC	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]


  

			
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	E.11	  	Initial submission to CA and EC	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.12	  	Regulatory maintenance—administrative amendments	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.13	  	Regulatory maintenance—substantial amendments	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 [***]

							
	E.14	  	Project Management—Regulatory Affairs	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 [***]

							
	E.15	  	Regulatory Manager—Teleconferences	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	E.16	  	Insurance arrangement	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	F	  	SITE SELECTION ACTIVITIES	  				  				  				  	 	[***]	  	  	
							
	F.1	  	Identify Investigative Sites	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 [***]

							
	F.2	  	Site Selection Visits—visits	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	F.3	  	Site Selection Visits—travelling	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G	  	MONITORING	  				  				  				  	 	[***]	  	  	
							
	G.1	  	Site Initiation Visits—visits	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G.2	  	Site Initiation Visits—travelling	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G.3	  	Interim Monitoring Visits—visits	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G.4	  	Interim Monitoring Visits—travelling	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G.5	  	Site Close-out Visits—visits	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	G.6	  	Site Close-out Visits—travelling	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	H	  	MEDICAL MONITORING	  				  				  				  	 	[***]	  	  	[***]
							
	I	  	SAFETY REPORTING	  				  				  				  	 	[***]	  	  	[***]
							
	J	  	DATA MANAGEMENT	  				  				  				  	 	[***]	  	  	[***]
							
	K	  	PROJECT MANAGEMENT	  				  				  				  	 	[***]	  	  	
							
	K.1	  	Project management	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]


  

			
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				  		  				  				  				  				  	[***]
							
	 	K.3	  	  	Internal team meetings—COPM participation	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	K.5	  	  	Internal team meetings—CRAs participation	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	K.6	  	  	Verification of monitoring reports	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	L	  	  	QUALITY ASSURANCE SERVICES	  				  				  				  	 	[***]	  	  	
							
	 	L.1	  	  	Quality assurance services—Clinical management	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
						
	 	CRO TOTAL	  				  				  	 	[***]	  	  	 	[***]	  	  	
							
	 	 	  	 ESTIMATED PASS THROUGH COSTS (this
is rough estimation of the majority costs
which
should be taken into account and not directly
paid by Sponsor)
	  	 	 	  	Unit
Cost
(€)	 	  	Quantity
of units	 	  	Total	 	  	 
							
	 	1	  	  	Regulatory costs	  				  				  				  	 	[***]	  	  	
							
	 	1.1	  	  	Ethics Committee fees + RA fee	  				  				  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	1.2	  	  	Custom clearance	  				  				  				  	 	[***]	  	  	[***]
							
	 	1.3	  	  	Insurance	  				  				  				  	 	[***]	  	  	[***]
	 	2	  	  	Travel costs	  				  				  				  	 	[***]	  	  	


  

			
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	 	2.1	  	  	CRA Travel (hotels, tickets, allowances)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	2.2	  	  	QAD Travel (hotels, tickets, allowances)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	2.3	  	  	Investigator Meetings travel and hotel costs (per attendee)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	2.4	  	  	Patients travel costs	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	3	  	  	Administration	  		  				  				  	 	[***]	  	  	
							
	 	3.1	  	  	Copies / duplication (binding and photocopies included)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	3.2	  	  	Courier / shipment	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	3.3	  	  	Telephone / fax	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	4	  	  	Translation	  		  				  				  	 	[***]	  	  	
							
	 	4.1	  	  	Translation of study documents	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	5.	  	  	Other costs	  		  				  				  	 	[***]	  	  	
							
	 	5.1	  	  	Overnight stay	  		  				  				  	 	[***]	  	  	[***]
						
	 	PASS-THROUGH COSTS TOTAL	  		  				  				  	 	[***]	  	  	
							
	 	 	  	 SERVICE PROVIDERS COSTS
	  	 	  	Unit
Cost
(€)	 	  	Quantity
of units	 	  	Total	 	  	 
							
	 	1	  	  	Central Laboratory	  		  				  				  	 	[***]	  	  	
							
	 	2	  	  	Data Management	  		  				  				  	 	[***]	  	  	
							
	 	3	  	  	Drug Supply	  		  				  				  	 	[***]	  	  	
							
	 	4	  	  	IVRS	  		  				  				  	 	[***]	  	  	
							
	 	5	  	  	Statistical Analysis and CSR	  		  				  				  	 	[***]	  	  	
						
	 	SERVICE PROVIDORS COSTS TOTAL	  		  				  				  	 	[***]	  	  	


  

			
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	 	 	  	 INVESTIGATORS FEES
	  	 	  	Unit
Cost
(€)	 	  	Quantity
of units	 	  	Total	 	  	 
	 	1	  	  		  		  				  				  	 	[***]	  	  	
							
	 	1.1	  	  	Investigators fee	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	1.2	  	  	Country study co-ordinator fees	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	1.3	  	  	Investigators fee (screen failures)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	1.4	  	  	Start-up fees (Polish sites)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
							
	 	1.5	  	  	Archiving fees (Polish sites)	  		  	 	[***]	  	  	 	[***]	  	  	 	[***]	  	  	[***]
						
	 	INVESTIGATORS FEES TOTAL	  		  				  				  	 	[***]	  	  	
		
	 	TOTAL CRO FEES	  	  	 [***]

		
	 	TOTAL PASS THROUGH COSTS	  	  	 [***]

		
	 	TOTAL VENDORS COSTS	  	  	 [***]

		
	 	TOTAL INVESTIGATORS FEES	  	  	 [***]

		
	  
	 PROJECT GRAND TOTAL
	   
	  	[***]


  

			
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