EXHIBIT 10.14
CLINICAL STUDY SUPPORT AGREEMENT
among
UNIVERSITY HOSPITALS OF CLEVELAND
and
CASE WESTERN RESERVE UNIVERSITY
and
OSIRIS THERAPEUTICS, INC.
This Agreement is executed as of October 28, 1996 by and among University
Hospitals of Cleveland, ("UHC" or "Institution"), Case Western Reserve
University ("CWRU") and Osiris Research, Inc. ("Osiris"), a wholly owned
subsidiary of Osiris Therapeutics, Inc.
WITNESSETH
WHEREAS, UHC proposes to conduct a Study of Protocol CWRU 1194 (the
"Protocol") entitled "Phase I Trial Using Bone Marrow-Derived Mesenchymal
Xxxxx Cells in Autologous Hematopoietic Stem Cell Transplantation for
Advanced Breast Cancer" (the "Study"), relating to the treatment of advanced
breast cancer patients by a combination of standardized medical procedures
and the infusion of autologous Mesenchymal Xxxxx Cells (MSCs, the "Study
Therapeutic Agent"); and
WHEREAS, the Protocol is an Investigator-initiated and sponsored study; and
WHEREAS, the Study Therapeutic Agent will be isolated, culture-expanded and
provided to the Study in CWRU facilities by CWRU staff; and
WHEREAS, Osiris wishes to enable the Principal Investigator and UHC to
sponsor and conduct the Study through a grant-in-aid to be provided by
Osiris; and
WHEREAS, Osiris may provide certain equipment and advice to the Investigators
and UHC relating to certain methods that might be used in the Study; and
WHEREAS, the Principal Investigator, UHC, CWRU, and Osiris mutually agree
that the Study will be performed and controlled by UHO personnel;
NOW THEREFORE, it is agreed as follows:
ARTICLE l. SUPERVISION
Xxxxxxx Lazams, M.D., as the Principal Investigator and representative of
UHO, shall have the responsibility for supervision of the Study in accordance
with the Protocol, and generally accepted standards of good clinical
practice, all applicable local, state, and federal laws and regulations
governing the performance of clinical investigators, and the regulations of
the United States Food and Drug Administration ("FDA").. The performance site
of this Study is University Hospitals of Cleveland, Ireland Cancer Center,
00000 Xxxxxx Xxxxxx, Xxxxxxxxx, Xxxx 00000.
ARTICLE 2. SCOPE OF WORK
Osiris shall provide the equipment listed on Exhibit C (the "Equipment") and
certain standardized methods as described in the FDA-approved Protocol. UHC
shall supply the necessary personnel: any other necessary equipment, and
materials (except as otherwise may be provided herein) to complete the
protocol (the "Protocol") (see Exhibit A - APPROVED PROTOCOL). CWRU shall
provide the necessary personnel to isolate and culture-expand the stem cells.
All procedures for directing and monitoring the Study are delineated in the
Protocol. Any change in the scope of work shall require the express written
approval of
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UHC, CWRU and Osiris. At the expiration or termination of the Study, the
Equipment shall become the sole property of CWRU, subject to the terms of
Article 23 herein.
ARTICLE 3. LIMITATION OF COSTS
Osiris shall provide financial support for the Study in an amount not to
exceed Three Hundred Thirty-Five Thousand Three Hundred Seventy-Six and
00/100 Dollars ($335,376.00) in accordance with the approved budget attached
hereto as Exhibit B - APPROVED BUDGET and incorporated herein by reference.
ARTICLE 4. METHOD OF PAYMENT
Osiris shall make all checks payable to University Hospitals of Cleveland and
forward them to the following address:
University Hospitals of Cleveland
Ireland Cancer Center, WRN 5065
00000 Xxxxxx Xxxxxx
Xxxxxxxxx, Xxxx 00000
Attention: Xxxxxxx Xxx
Institution Tax Identification Number: 34-1 567805
For purposes of identification, each payment shall include the title of the
Study and the name of the Principal. Investigator.
Osiris shall make payments to UHC according to the payment schedule in
Exhibit B - APPROVED BUDGET referenced above.
An initial advance of twenty five percent (25%) of the total budget,
Eighty-Three Thousand Eight Hundred Forty-Four and 00/100 Dollars
($83,844.00) shall be made to UHO upon execution of this Agreement.
Subsequent quarterly payments of Eighty-Three Thousand Eight Hundred
Forty-Four and 00/100 Dollars ($83,844.00) shall be due and paid at the
beginning of each subsequent quarter (January, 1997, April, 1997, and July,
1997). The Budget is based on enrollment of twenty-five (25) patients in the
Study over the twelve (12) month period. In the event that the Study is not
completed during the designated time period, additional funding will be
provided to UHC by Osiris to cover the personnel costs associated with the
Cell Culture component of the Budget and such additional funding shall be
computed using the same percentage as the effort specified in the Budget
until the accrual goal is met.
Partial payment for Study Subject(s) who do not complete the Protocol and/or
are lost to follow up will be made in accordance with Exhibit B.
ARTICLE 5. INDEPENDENT CONTRACTOR
Osiris, CWRU, and UHC are independent contractors, and this Agreement shall
not be construed to constitute a partnership or joint venture between them or
make either party the agent or employee of the other. No party shall hold
itself out contrary to the terms of this provision, and no party shall become
liable for any representation, act or omission of any other party contrary to
the terms hereof.
ARTICLE 6. CONFIDENTIALITY
Nothing in this Agreement shall be construed to limit the freedom of
individuals participating in this Study, whether paid under this Agreement or
not, to engage in similar research independently under other grants,
contracts, or agreements with parties other than Osiris.
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CWRU, UHC and Principal Investigator acknowledge that Osiris may provide,
during the course of the Study, certain information that Osiris deems
confidential. Osiris shall clearly label, in writing, all of that information
provided in writing that it considers confidential ("Confidential
Information"). CWRU, UHC and Principal Investigator agree to use reasonable
efforts to prevent disclosure or unauthorized use of Confidential Information
without Osiris's prior written consent; provided, however, that Confidential
Information shall not include that information which:
(i) is now or hereafter becomes part of the public domain through no
fault of CWRU, UHC or the Principal Investigator;
(ii) is known to CWRU, UHC or the Principal Investigator before the
effective date of this Agreement;
(iii) is obtained by CWRU, UHC or the Principal Investigator from a
third party without that party's breach of confidentiality obligations;
(iv) is independently developed by CWRU, UHC or Principal Investigator
for UHC; or.
(v) is required to be disclosed pursuant to law, regulation or court
order.
ARTICLE 7. PUBLICATION
Notwithstanding any other provision contained in this Agreement, the
Principal Investigator shall have the right, at his/her discretion, to
publish freely, in scientific journals, the clinical data generated from this
Study. The Principal Investigator shall furnish Osiris with a copy of any
proposed publication of material at least thirty (30) days in advance of the
proposed publication date.
The Principal Investigator shall respond, in good faith, to any suggested
revisions of the manuscript.
The Principal Investigator shall give Osiris the option of receiving
acknowledgment for its financial support in such publications.
ARTICLE 8. PATENTS
"Invention or Discovery" shall mean any invention or discovery conceived and
reduced to practice during and as a part of the Study performed pursuant to
this Agreement by Principal Investigator or other CWRU faculty, UHC's or CWRU
staff or employees, or CWRU's students or jointly by such an individual or
individuals with one or more employees of Osiris. Inventions or Discoveries
made solely by Institution's staff or employees shall be the sole property of
the Institution or its designated agent. New Inventions or Discoveries made
jointly by Institution's staff or employees with one or more employees of
Osiris shall be owned jointly by the Institution and Osiris. Inventions or
Discoveries made solely by Osiris shall be the sole property of Osiris.
Inventions or Discoveries made solely by CWRU's faculty, including the
Principal Investigator, employees, or students shall be the sole property of
CWRU or its designated agent. Inventions or Discoveries made jointly by
CWRU's faculty, including Principal Investigator, employees or students with
one or more employees of Osiris shall be owned jointly by CWRU and Osiris.
ARTICLE 9. DATA
UHC shall provide copies of the clinical results of the Study to Osiris and
CWRU at the same time such results are submitted to the FDA. The Institution
and CWRU shall retain all records resulting from the Study for the time
required by applicable federal regulations and allow for inspection of all
such records. Osiris shall notify the Institution of the FDA Application
filing and approval status.
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ARTICLE 10. PUBLICITY
No party shall use, nor authorize others to use, the name, symbols, and/or
marks of another party in any form of advertising or publicity material or
make any form of representation or statement in connection with the services
and/or studies which would constitute an expressed or implied endorsement by
another party of any commercial product or service. This prohibition shall
not include documents or legally required disclosure by UHC, CWRU or Osiris
that identifies the existence of the Agreement. Further, Osiris agrees that
its use of the name, symbols, and/or marks of UHC or CWRU or names of UHC's
employees or CWRU's employees, shall be limited to identification of UHC and
CWRU as a research site and research staff as participants in the research
required by law or regulation.
ARTICLE 11. HUMAN SUBJECTS
UHC agrees that this Protocol has been approved by the appropriate UHC
Institutional Review Board (x C - HUMAN SUBJECTS APPROVAL). The Principal
Investigator shall obtain from each of the participants written informed
consent in compliance with 21 CFR 50.20 through 50.27.
ARTICLE 12. INDEMNIFICATION
Osiris agrees to indemnify, defend and hold harmless UHC and CWRU and their
respective employees, agents, officers, trustees, Principal Investigator, and
University Physicians, Inc., and other qualified personnel working under
their direct supervision in the performance of the Study (collectively, the
"Indemnitees"), from and against any claims, causes of action, suits,
liability, damage, and costs that are based on assertions of personal injury
or property damages sustained as a result of the use or misuse of the
clinical results of the Study by Osiris, its employees, and agents or the
negligence or misconduct of Osiris, its employees, and agents, and Osiris
will pay any costs, expenses, and reasonable attorney's fees in connection
therewith without regard to whether such claims, causes of actions or suits
are rightfully or wrongfully brought and without regard to any determination
of liability.
UHC agrees to indemnify, defend and hold harmless CWRU, Osiris, its
employees, agents, officers, trustees, and other qualified personnel working
under their direct supervision in the performance of the Study (collectively,
the "Osiris Indemnities"), from and against any claims, causes of action,
suits, liability, damage, and costs that are based on assertions of personal
injury or property damages sustained as a result of negligence or misconduct
of UHC, its employees, and agents, and UHC will pay any costs, expenses, and
reasonable attorney's fees in connection therewith without regard to whether
such claims, causes of actions or suits are rightfully or wrongfully brought
and without regard to any determination of liability.
A party seeking indemnification shall provide the indemnifying party prompt
notice of any claim for which indemnification will be sought, will cooperate
in the investigation and defense of such claim, will permit the indemnifying
party to direct the defense of such claim, including selecting counsel, and
will not settle or compromise any such claim without the indemnifying party's
prior written approval. The indemnifying party shall reasonably consult with
the party seeking indemnification prior to settling claims. The indemnifying
party shall not, except with the consent of the party seeking
indemnification, consent to entry of any judgment or enter into any
settlement which does not include an unconditional release of the Indemnitees
or the Osiris Indemnitees, as the case may be, from all liability in respect
of such claim or litigation.
Except as otherwise provided herein, UHC agrees not to seek recovery from
either CWRU or Osiris for any cost or expense associated with providing
reasonable and necessary medical diagnosis and treatment associated with any
adverse reactions.
ARTICLE 13. INSURANCE
Osiris agrees to carry sufficient liability insurance to cover its
obligations hereunder. Evidence of coverage satisfactory to UHC and CWRU
shall be delivered to UHC and CWRU with the signature of this Agreement.
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Osiris certifies that it will not terminate, fail to renew or materially
reduce its coverage without 45 days advance written notice to UHC and CWRU.
UHC represents and warrants that it maintains self-insurance in such amounts
sufficient to cover its indemnification obligations under this Agreement.
ARTICLE 14. TERM AND TERMINATION
This Agreement shall continue from the date of signing until completion of
the approved Protocol, unless terminated earlier as provided herein. UHC
shall retain ownership of all property unless otherwise designated and
accepted in writing; provided, however, that CWRU shall retain ownership of
all the Equipment.
This Study may be terminated for any reason by UHC or Osiris, the UHC
Institutional Review Board, or the FDA, when appropriate. In the event of
early termination of this Agreement, UHC shall provide medical treatment, to
then enrolled patients as required by accepted medical practice, which
treatment may include completion of the Study if required by accepted medical
practice.
The provisions of Articles 9, 12, and 13 shall survive the termination of
this Agreement.
ARTICLE 15. MODIFICATION
Any alteration in or amendment to the Protocol or to this Agreement must be
in writing and approved by UHC, the Principal Investigator, and Osiris prior
to such alteration or amendment becoming effective.
ARTICLE 16. CONTACTS
The UHC scientific contact for this Agreement will be the Principal
Investigator
Xxxxxxx Xxxxxxx, M.D.
University Hospitals of Cleveland
Ireland Cancer Center
00000 Xxxxxx Xxxxxx
Xxxxxxxxx, Xxxx 00000-0000
Phone: (000) 000-0000
Fax: (000) 000-0000
The UHC administrative contact for this Agreement will be:
Xxxxxxx X. Guy, Ph.D.
Associate Director
Ireland Cancer Center
University Hospitals of Cleveland
00000 Xxxxxx Xxxxxx
Xxxxxxxxx, Xxxx 00000-0000
Phone: (000) 000-0000
Fax: (000) 000-0000
The Osiris contact for this Agreement will be:
Xxxxx X. Xxxx, Ph.D.
Director, Clinical Research Liaison
Osiris Therapeutics, Inc.
0000 Xxxxxxxxx Xxxxxx
Xxxxxxxxx, Xxxxxxxx 00000-0000
Phone: (000) 000-0000
Fax: (000) 000-0000
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The CWRU contact for this Agreement will be:
Xxxxxx Xxxxxxxx
Assistant Director, Research Administration
Xxxxxxxx Xxxx, Room 4
Case Western Reserve University
School of Medicine
Xxxxxxxxx, Xxxx 00000-0000
All notices shall be given in writing and delivered in person or by certified
or registered U.S. mail to the respective addresses above.
ARTICLE 17. GOVERNING LAW
This agreement shall be governed by and construed in accordance with the laws
of the State of Ohio.
ARTICLE 18. ENTIRE AGREEMENT
This Agreement, together with the Protocol and referenced exhibits, contains
the entire agreement of the parties with respect to the subject matter
hereof, and supersedes all previous and contemporaneous agreements and
understanding, whether oral or written, between the parties.
ARTICLE 19. REPORTING OF DATA
Principal Investigator and UHC agree to provide Osiris periodically and in a
timely manner during the term of this Agreement with the data called for in
the Protocol on properly completed case reporting forms.
ARTICLE 20. COMPLIANCE WITH LAW AND ACCEPTED PRACTICE
Principal Investigator and Institution shall perform the Study in conformance
with generally accepted standards of good clinical practice, with the
Protocol, instructions provided by Osiris and with all applicable local,
state and federal laws and regulations governing the performance of clinical
investigations including, but not limited to, the Federal Food, Drug and
Cosmetic Act and regulations of the Food and Drug Administration.
ARTICLE 21. MONITORING OF STUDY
During the term of this Agreement, CWRU, UHC, and Principal Investigator
agree to permit representatives of Osiris and or the FDA to examine at any
reasonable time during normal business hours:
i) the facilities where the Study is being conducted;
ii) raw Study data including original patient records (subject to
legal restrictions relating to patient confidentiality); and
iii) any other relevant information necessary to confirm that the Study
is being conducted in conformance with the Protocol and in
compliance with applicable FDA and DEA laws and regulations. UHC
shall notify Osiris if FDA or DEA schedules or, without scheduling,
begins an inspection.
ARTICLE 22. WAIVER
No waiver of any term1 provision or condition of this Agreement whether by
conduct or otherwise in any one or more instances shall be deemed to be or
construed as a further or continuing waiver of any such
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term, provision, or conditions, or of any other term, provision or condition
of this Agreement.
ARTICLE 23. EQUIPMENT
Osiris has provided the Equipment listed in Exhibit C for use during the
Study to culture autologous MSCs. The equipment is currently in operation in
Room W517 of the CWRU School of Medicine. Osiris intent in providing this
Equipment is to permit CWRU personnel to prepare culture-expand autologous
MSCs in an appropriate clean-room environment for the subject Study and
future studies in which autologous MSCs might be tested for treatment of the
same disease or other clinical indications. Upon termination of this
Agreement, title to all such Equipment owned by Osiris shall be transferred
to CWRU in good working order, free of all liens, as compensation for use of
the facility for the subject Study and future clinical studies requiring MSCs.
CWRU acknowledges that some or all of the equipment installed in this
facility has been leased to Osiris under a Master Lease Agreement dated as of
February 1, 1994 between Osiris and Dominion Ventures, Inc. (the "Lease
Agreement"), and that Osiris will have the option to buy such equipment at
the end of the lease term for the fair market value of the equipment, as
determined under the Lease Agreement with respect to such equipment. At the
end of the lease term, CWRU agrees to cooperate with Osiris in surrendering
such equipment and Osiris shall surrender such equipment to Dominion Ventures
unless CWRU agrees to pay Dominion Ventures the fair market value in exchange
for title to the equipment in accordance with the terms of the Lease
Agreement. A detailed list of equipment included is attached hereto as
Exhibit C.
CWRU agrees that the room containing the Equipment shall be available for
the culture of autologous MSCs for use in clinical trials, including the
subject Study and future studies that might be supported in part by Osiris.
Availability of this room for MSC culture shall be consistent with CWRU
policies and shall be for a period of three (3) years from the initiation of
the subject Study, except if Osiris at its sole discretion, shall inform CWRU
that it is no longer interested in supporting such studies. Osiris and CWRU
further agree that a plaque bearing the name of the facility (Mesenchymal
Stem Cell Culture Facility") shall be placed on the exterior wall of Room
W517 at Osiris' expense, and that the plaque shall also bear the inscription,
at the option of Osiris, "Partially supported by Osiris Therapeutics, Inc.".
[Remainder of page intentionally left blank; signatures begin on next page.]
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UNIVERSITY HOSPITALS OF CLEVELAND
/s/ M. Xxxx Xxxxxx
---------------------------------
M. Xxxx Xxxxxx
Executive Vice President
10/28/96
---------------------------------
Date
OSIRIS THERAPEUTICS, INC.
/s/ Xxxxx X. Xxxxx
---------------------------------
Xxxxx X. Xxxxx
President & Chief Executive Officer
11/4/96
---------------------------------
Date
CASE WESTERN RESERVE UNIVERSITY
/s/ Xxxxxxx X Xxxxxx
---------------------------------
Signature
Xxxxxxx X. Xxxxxx
---------------------------------
Printed Name
Xxxxxxx
---------------------------------
Title
10/29/96
---------------------------------
Date
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