Agreement for ClinicalTrials (withoutCRO)

a.

The Company has expressed its interest in managing the Clinical Trial, the subject of which is “Safety and Efficacy of Sustained Erythropoietin Therapy of Anemia in Chronic Kidney Disease Patients using EPODURE Biopump” (hereinafter: the “Trial”), with Company’s code name “EPODURE Trial”, bearing protocol No. MG-001-02, a copy of which is attached as Appendix A hereto (hereinafter: the “Trial Protocol”); and

b.

The Company has warranted that to the best of its knowledge it is either the sole owner of, or has license to, the intellectual property rights in the Product, as defined below, and the Trial Protocol, and there is no prohibition under any law and/or agreement to the Company executing this Agreement and performing its obligations hereunder in all material respects; and

c.

The Fund and the Principal Investigator have the ability, the facilities and the staff to perform the Trial, and the Fund and the Principal Investigator have agreed to perform the Trial, without any promise of success. The Fund and the Principal Investigator have warranted that there is no prohibition under any law and/or agreement to the Fund or the Principal Investigator executing this Agreement and performing their respective obligations hereunder in all material respects; and

d.

The Company has agreed to pay the Fund the consideration, specified in Appendix C hereto, for the performance of the undertakings of the Principal Investigator and the Fund under this Agreement; and

e.

The Company shall not pay the Principal Investigator any consideration, it being agreed that the Principal Investigator will conduct the Trial under the auspices of the Fund and in consideration of whatever compensation the Fund will pay to the Principal Investigator pursuant to a separate agreement among them.

1.

 

a.

The preamble to this Agreement and the representations contained therein constitute an integral part of the Agreement.

 

b.

The appendices appended to this Agreement, as specified hereunder, constitute an integral part of the Agreement: - -

 

c.

The provisions of this Agreement shall prevail - in the event of a contradiction or non-compliance - over the provisions of any appendix attached to this Agreement or which shall be attached hereto in the future, unless said appendix explicitly provides that its provisions shall prevail over this Agreement. However, existing and/or future Ministry of Health regulations and/or guidelines shall prevail over the provisions of this Agreement and/or any appendix provided that said regulations and/or guidelines are stricter regarding the Company’s undertakings than the Company’s undertakings under this Agreement and/or any appendix.

2.

3.

 

3.1

Upon signing this Agreement, the Company appoints the Fund and the Principal Investigator, and those two parties undertake, each of them pursuant to its authority and share, to perform the Trial according to the stages thereof, within the framework and by means of the Hospital and to provide all needed facilities, materials and services necessary to complete the Trial, while complying with the schedule, the Trial budget and the Trial Protocol in Appendix “A”, and while complying with the demands and terms established by the Ministry of Health, and all pursuant to the terms and conditions of this Agreement. The Fund shall be responsible for and obtain all approvals required under any applicable law for the conduct of the Trial.

 

3.2

Notwithstanding sub-section 3.1 above, in the event that the employer-employee relationship between the Principal Investigator and the Hospital and/or the Fund is terminated for any reason and/or in the event the Principal Investigator goes on leave and/or is unable and/or unwilling to carry out his duties under this Agreement, for any reason, the Fund may appoint a substitute Principal Investigator in place of the Principal Investigator subject to the prior written approval of the Company, which shall not unreasonably be withheld.

4.

 

4.1

Subject to the terms of this Agreement, the Term of the Agreement shall be the duration of the Trial as defined in the Trial Protocol, which shall commence on                                 and end upon completion of the Trial; provided, however, that the rights and obligations under Sections 5.6, 6, 8, 9, 10, 11, 12 and 15 shall survive the termination or expiration of this Agreement.

 

4.2

Notwithstanding the aforesaid in sub-section 4.1 above, but subject to the provisions that survive termination, the Parties may bring this Agreement to an early end at any time, in writing, upon the occurrence of one (or more) of the following events: -

 

4.2.1

by the Company only, at any time at its sole discretion, by way of a written notice to the Fund, thirty (30) days in advance.

 

4.2.2

if the Ministry of Health has voided, directly or indirectly, its approval of the Trial or has conditioned its approval on conditions, as to which the Fund has notified the Company that it does not intend and/or is unable to comply with these conditions in whole or in part. In such case the Agreement shall be terminated not later than ten (10) days after such notice shall have been sent to the Company.

 

4.2.3

A Party breaches this Agreement and does not cure such breach within thirty (30) days after having received a notice in writing from the other Party demanding a cure of the breach in reasonable detail so that the breaching Party is on notice of the nature of the breach.

 

4.2.4

A party enters into bankruptcy or liquidation proceedings or a receiver is appointed over part or all of its assets, and such proceedings are not ceased within a period of forty five (45) days from the time that they have commenced.

 

4.2.5

An adverse effect occurs to the Participants in the Trial, which, in the absolute discretion of the Fund and/or the Principal Investigator and/or the IRB, jeopardizes the safety of the Participants in the Trial and/or the Trial Personnel, and prior notice thereof is given immediately to the Company by any member of the Trial Personnel and the Principal Investigator within a reasonable time from the discovery of such adverse effect. In such case the Agreement shall be terminated immediately after such notice shall be sent.

 

4.3

For the avoidance of any doubt, the termination of this Agreement, for any reason, shall not prejudice the Company’s undertaking to pay the Fund for all services and expenditures of the Fund under this Agreement until the termination of the Agreement.

5.

 

5.1

The Company shall supply to the Principal Investigator the Products and/or parts of the Product and/or the materials from which the Product is composed, without consideration, at the necessary pharmaceutical standard, all in accordance with the schedule and in the quantities provided in the Trial Protocol.

 

5.2

The Trial shall be performed and managed by the Principal Investigator at the Hospital facilities, while making use of the Hospital’s resources, without payment of further consideration by the Company therefore.

 

5.3

The Principal Investigator shall carry out the Trial in accordance with the Trial Protocol, GCP, and all the relevant laws and regulations prevailing in Israel and in accordance with all necessary permits and/or licenses from the relevant authorities.

 

5.4

In performance of the Trial, the Fund shall employ, directly or indirectly, the Trial Personnel, which will comprise the individuals specified in the list appended herewith and marked as Appendix B to this Agreement. In the event that any of the Trial Personnel so identified cease to be available for the Trial, the Fund will use its best efforts to procure within 30 days a substitute of a suitably qualified person acceptable to the Company. The Fund and the Principal Investigator represent and warrant that none of the Trial personnel has been debarred, disqualified or banned from conducting clinical studies by any regulatory agency, including the Israeli Ministry of Health and the U.S. Food & Drug Administration. In the event that prior to or during the Trial, the Fund or the Principal Investigator become aware that any of the Trial Personnel becomes disbarred, or is in the process of disbarment, the Fund will immediately notify the Company in writing and the Fund will procure within 30 days a substitute of a suitably qualified person acceptable to the Company.

 

5.5

Subject to the provisions of sub-section 11 below, the representatives of the Company shall have the right to examine the results, notes and other documents and representations obtained during the course of the Trial, during regular working hours and confidentially inspect the Principal Investigator’s and the Hospital’s facilities required for performance of the Trial, after providing advanced written notice and at a reasonable time.

 

5.6

In performance of the Trial, pursuant to this Agreement, the Company undertakes to continue to supply the Product to the Fund and/or the Hospital, without consideration, in order to complete the commenced treatment of the Participants of the Trial at the Principal Investigator’s sole and reasonable discretion, or as part of the Trial Protocol, should one of the Participants of the Trial become dependent on the Product.

 

5.7

Notwithstanding the Company’s undertakings under this Agreement, the Company undertakes to abide by all the relevant laws and regulations prevailing in Israel and in accordance with and after all necessary permits and/or licenses from the relevant authorities, as are presented to it by the Fund.

6.

 

6.1

The Principal Investigator shall meet with the representatives of the Company, during the customary working hours and to a reasonable extent, in order to report to the Company, on an ongoing and consecutive basis, and in order to update the Company in all matters related to the performance of the Trial, its progress, difficulties, solutions, etc. The Principal Investigator shall promptly advise the Company of any serious adverse event or unanticipated effect occurring during the Trial, or subsequent to the completion or termination of the Study, that becomes known to him.

 

6.2

The Principal Investigator shall prepare and maintain reasonably complete and accurate written records, accounts, notes, report and data of the Trial, including case report forms. The Principal Investigator shall prepare the case reports forms (CRF) legibly and accurately (or ensure that a co-Investigator does so) throughout the Trial, and shall make the CRF available to the Company. The Principal Investigator will retain or will cause the Fund to retain all such materials and data that the Fund has to retain under any applicable law for such periods as such law determines.

 

6.3

The Principal Investigator hereby undertakes to adhere to the accuracy of the Trial results as required by the Helsinki Declaration and the GCP.

7.

 

7.1

In consideration for the performance of the Trial under this Agreement, the Company shall pay the Fund the consideration specified in Appendix C to this Agreement on the dates specified in Appendix C. Such payments shall be made against a proper invoice render a reasonable time in advance of the due date for the payment.

 

7.2

To avoid any doubt, it is hereby clarified that the Fund and/or the Principal Investigator shall not perform any acts which deviate from the acts specified in the Trial Protocol and/or are specifically mentioned in this Agreement unless the Fund and the Company have both approved said acts, in advance and in writing.

8.

 

8.1

The Company shall indemnify and hold harmless the Hospital, the Fund, the Principal Investigator, the Trial Personnel and all other employees of the Hospital and the Fund (hereinafter: the “Indemnitees”) from and against any loss, damage, liability and expense (including legal costs) arising out of or resulting, directly or indirectly, from the use of the Products and/or any other materials which have been supplied by the Company and/or from conducting the Trial in accordance with the Trial Protocol, except to the extent that such loss, damage, liability or expense are a result of the negligent acts, willfulness, misconduct or breach of contract of any of the Fund, the Principal Investigator or the Trial Personnel.

 

8.1.1

The indemnity shall not apply in case of claims or losses arising from a breach of the Trial Protocol, GCP, Helsinki Declaration, National Health Regulations, and/or any other applicable law or regulation relating to the Trial.

 

8.1.2

The Company will be notified promptly and in writing of any complaint or claim promptly after the Fund becomes aware of the same.

 

8.1.3

The Company will be given absolute and sole discretion in the defense and settlement of any such complaint or claim.

 

8.1.4

The Fund shall cooperate with and give the Company reasonable assistance in connection with any such claim or proceedings at Company’s cost and expense, and shall consent to any reasonable settlement of such complaint or claim approved by the Company.

 

8.2

Without derogation from Company’s liability under this Agreement and/or under any applicable law, including the Ministry of Health Directive, Company undertakes to present the Fund an Insurance Certificate according to the law of Israel and the Guidelines of the Ministry of Health. The Certificate will specifically include the following provisions:

 

8.5.

The Company hereby undertakes that any and all settlements of indemnification claims hereunder by the Company and/or its insurers will be free of admission of any liability whatsoever on the part of the Indemnitees.

 

8.6.

The Company’s undertaking under this section shall survive termination of this Agreement for whatever reason.

9.

Limitation of Liability. The Parties agree that the Parties shall be liable for direct damages only and that no Party shall be liable for indirect, incidental or consequential damages in connection with the Agreement.

10.

11.

12.

 

12.1

The Fund and the Principal Investigator undertake to keep, and shall cause all other Trial Personnel to keep, in absolute confidence, not to transfer or disclose to any person and/or entity and not to make any use, other than for purposes of the performance of the Trial, any information, data, inventions, conceptions, results, or know-how, whether orally or in writing, which shall come into their possession in relation to and/or in connection with the Trial, the Trial Results and/or the Product and/or the IP (hereinafter - the Confidential Information).

 

12.2

It is hereby clarified that submission of the Confidential Information pursuant to the demands of the authorities operating by virtue of the law and according to their authority, after prior written notice has been delivered with respect to same to the Company, as well as the exposure of Confidential Information, after it has become public domain, but not as a result of its being published in a patent application or granted patent, and not as a result of the acts and omissions of the Hospital, the Fund, the Principal Investigator and/or any other Trial Personnel, shall not be considered a breach of this Agreement.

 

12.3

At the request of the Company, the Principal Investigator or the Fund, as the case may be, will return to the Company all copies or other manifestations of Confidential Information that may be in the possession of the Principal Investigator or the Fund, except for materials that have to be retained by the Principal Investigator or the Fund in accordance with applicable law.

13.

 

13.1

The Principal Investigator and the Fund hereby undertake to submit to the Company all drafts of any publications proposed for publication by the Principal Investigator, no later than sixty (60) days prior to the submission of any form of such publication or drafts thereof to any journal, publisher, and/or any other third party.

 

13.2

The Company hereby undertakes to promptly inform the Principal Investigator and the Fund of any changes and/or deletions the Principal Investigator is to perform in such publications, required for the purpose of preserving the confidentiality and proprietary rights of the Company under this Agreement. It is agreed that the Principal Investigator and/or the Fund shall not make any publication of information to which the Company objects under this sub-section 12.2.

 

13.3

Without derogating from the above, the Company hereby undertakes to abide by the rules of publications issued by the Ministry of Health including and without limitation the Guidelines for the Conduct of Clinical Trials in Human Subjects issued by the Israeli Ministry of Health in 2006, or any guidelines issued in addition thereto or in substitution thereof.

 

13.4

As a condition for performing the Trial, the Company shall be responsible for publishing the Trial in the NIH web sites in accordance with the instructions of the General Manager of the Israeli Ministry of Health published in 4/9/05.

14.

15.

 

15.1

 

15.2

Approval of this Agreement in general and its Budget by the Ministry of Health and specifically by the Contracting Committee of the Ministry of Health.

 

15.3

Pursuant to section 8.5 of this Agreement, a written Confirmation of Insurance shall be provided to the Fund.

16.

 

16.1

This Agreement shall be exclusively governed by the Laws of the State of Israel.

 

16.2

Any dispute, controversy or claim arising under, out of or relating to this Agreement (and subsequent amendments thereof), its validity, binding effect, interpretation, performance, breach or termination, including tort claims, shall be exclusively referred to the competent courts in Tel Aviv, Israel.

17.

18.

19.

20.

 

20.1

Notwithstanding the aforesaid in this Agreement, a delay in the performance of an obligation imposed on any Party due to an event which falls under the definition of the term “Force Majeure” shall not be considered a breach of the Agreement, and performance of the said obligation shall be deferred until a date when the hindrance is removed, whereas the schedule will be amended accordingly, unless the performance has become, due to the delay, unreasonable under the circumstance of the matter.

 

20.2

For purposes of this Agreement, the term “Force Majeure” shall mean acts of war, acts of terror, sabotage, general conscription, decisions of legal tribunals (including injunctions, whether temporary or permanent), the acts and omissions of an authority operating pursuant to law, statute, strikes, state of emergency at the Hospital, and general stoppage of the economy, natural disasters and other events that are not under the reasonable control of the Party alleging the occurrence of the “Force Majeure” event if that same Party alleging the occurrence of the said “Force Majeure” event has taken all reasonable measures to prevent their occurrence and/or continuance.

21.

 

21.1

Any change or addition to this Agreement shall be made in writing and with the signatures of all of the Parties affected by said change or addition only.

 

21.2

In the event it is determined that any provision of this Agreement - which does not constitute a material and basic term herein - is invalid, illegal or unenforceable, this will be insufficient to cause the avoidance of the rest of the provisions of this Agreement and/or to affect the validity, legality or the possibility of the enforcement of the rest of the provisions, as stated.

 

21.3

This Agreement shall replace any prior binder, representation, engagement, arrangement or agreement between the parties, the subject matter of which is the Trial, and voids them to the extent that they exist.

22.

 

22.1

The addresses of the Parties for purposes of this Agreement shall be: -

 

22.2

A Party who shall change its address will submit notice of the same within a reasonable time to the other Parties.

 

22.3

A notice that must be submitted pursuant to this Agreement will be delivered to the Parties at the addresses specified above, by personal delivery.

 

22.4

Any notice submitted in accordance with this section shall be considered as if delivered to its address after the passing of one business day from the date on which receipt has been confirmed.

1.

Dr. Doron Swartz – Principle Investigator

2.

Dr. Gil Tzarnin – sub Principle Investigator

3.

Prof. Don Silverberg – sub Principle Investigator

4.

Ofer Rap – Site Study Coordinator

 

1.

On receipt of invoice, Net +30 days

 

2.

For each patient recruited into the trial, the Company will be invoiced:

 

a.

60% at patient enrollment

 

b.

40% at patient termination (or completion of 6 months of follow-up)

 

c.

Extended follow-up: invoiced on a quarterly basis

 

d.

Patient reimbursement will be charged to the Company without overhead, invoiced on a quarterly basis