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EXHIBIT 10.14
NORTHWEST BIOTHERAPEUTICS, INC.
CLINICAL TRIAL AGREEMENT
This Clinical Trial Agreement (the "Agreement"), is made as of the 16th
day of December, 1999, (the "Effective Date") by and between Northwest
Biotherapeutics, Inc., a Delaware corporation (the "Sponsor"), and The
University of Texas, M.D. Xxxxxxxx Cancer Center, a nonprofit educational and
healthcare facility having corporate powers under the laws of the State of Texas
(hereinafter the "Institution"), a component of The University of Texas System
(hereinafter the "System.")
RECITALS
The Sponsor desires to test its therapy of autologous recombinant
prostate specific membrane antigen loaded dendritic cells (the "Product") for
metastatic, hormone refractory prostate cancer in a clinical setting. The
Institution seeks the advancement of health care through research and clinical
investigation, and as such is willing to permit testing of the Product in
accordance with the terms of this Agreement.
AGREEMENT
In consideration of the foregoing and of the mutual promises contained
in this Agreement, the parties agree as follows:
1. STATEMENT OF WORK. The Institution agrees to conduct a clinical study
of the Product in accordance with study protocol No. DC1-HRPC attached hereto as
Exhibit A (the "Study"). In the event of any conflict between Exhibit A and the
provisions of this Agreement, the provisions of this Agreement shall govern.
2. PRINCIPAL INVESTIGATOR. The Study will be conducted under the direct
supervision of Xxxxxxxx Xxxxxxxxxx, M.D., Ph.D., Study Chairman (hereinafter the
"Principal Investigator") with the participation of other Institution clinical
and research personnel to be identified or approved by Sponsor. The Institution
agrees to conduct the Study in strict accordance with the protocol and all
applicable federal, state, and local laws and regulations. If Principal
Investigator becomes permanently unavailable, for any reason, the Sponsor may,
at its sole discretion, appoint another Principal Investigator or terminate this
Agreement.
3. IRB APPROVAL. The Institution's obligations to conduct the Study are
expressly conditional upon the approval of its Investigational Review Board,
which the parties and the Principal Investigator will cooperate to obtain. The
implementation of DC1-HRPC at the Institution is embodied in the IRB approved
Institutional Protocol ID99-333 attached hereto as Exhibit B. The Sponsor and
the Study Chair will closely coordinate to insure the FDA approved IND protocol
governing this trial (DC1-HRPC as approved by the FDA as described in the
"Investigator's Brochure," section V of the IND) and the ID99-333 protocol are
executed, maintained and amended in accordance with applicable Federal, State
and Institutional Regulations.
CONFIDENTIAL
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4. REPORTS AND CONFERENCES.
A. The Principal Investigator will make informal verbal reports
to the Sponsor (or the Sponsor's representatives) at least monthly, and will
meet with the Sponsor's representatives upon reasonable request at the
Institution's facilities to discuss the progress of the Study. A final written
report shall be submitted to the Sponsor within thirty (30) days after
completion of, or any premature termination of, the Study and, if requested, the
Principal investigator shall assist the Sponsor in interpreting such report.
Copies of all clinical data, including copies of case report forms,
questionnaires, other records identified in the Protocol and other relevant
information generated during the Study will be promptly and fully provided to
the Sponsor (or the Sponsor's representative), and shall be freely usable by the
Sponsor consistent with good business judgment.
B. The Institution agrees to notify the Sponsor within
twenty-four (24) hours after learning of any serious and/or unexpected adverse
Product reaction affecting any patient in the Study. The Institution further
agrees to follow up such notification of adverse Product reaction with
appropriate reports in compliance with the Protocol and all applicable legal and
regulatory requirements.
C. The Institution agrees to notify the Sponsor within
twenty-four hours in the event that the FDA or any other regulatory authority
notifies the Institution of a pending inspection/audit. In addition, the
Principal Investigator will forward to the Sponsor any written communication
related to the use of the Sponsor's Product received as a result of the
inspection/audit within twenty-four (24) hours of receipt of such communication
and will allow the Sponsor to assist in responding to any citations. Such
responses shall be made within two (2) weeks of issuance of any citations or
within any earlier deadline set by the issuing regulatory authority. The
Principal Investigator shall also provide to the Sponsor copies of any documents
provided to any inspector or auditor. In the event of the FDA or other
regulatory authority requests or requires any action to be taken to address any
citations, the Institution agrees, following consultation with the Sponsor, to
take such action as necessary to address such citations, and agree to cooperate
with the Sponsor with respect to any such citation and/or action taken.
5. PAYMENTS. The Sponsor will pay, to the Institution, as the
Institution's total compensation under this Agreement, the amounts and in
accordance with the schedule set forth in Exhibit C attached hereto.
6. PUBLICITY. Neither party shall use the name of the other party,
including any trademark, trade name, or any contraction, abbreviation,
simulation, or adaptation thereof of the other party, or the name of the party's
employees, in any publicity, advertising or news release without the prior
written approval of an authorized officer of the other party.
7. CONFIDENTIAL INFORMATION. During the performance of the Study and
during the term of this Agreement, the Institution or the Principal Investigator
may receive confidential or trade secret information, including information
concerning the Sponsor's present and future business, marketing plans,
regulatory submissions, product fines, product plans, date testing and research
techniques, inventions, processes, practices, trade secrets, and like
information
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(collectively, "Confidential Information") from the Sponsor. The Institution
agrees to hold in confidence all such Confidential Information and not to
disclose or make such Confidential information available to any third parties
without the Sponsor's written permission, for a period of five (5) years from
the termination of this Agreement. This obligation will apply only to
information which the Sponsor has designated in writing as "confidential" and
will not apply to any such information which:
(i) was known to the Institution prior to its receipt from the
Sponsor, as evidenced by written documentation;
(ii) was or becomes a matter of public information or publicly
available through no fault on the part of the Institution.
(iii) is acquired from a third party entitled to disclose the
information to the Institution; or
(iv) was developed independently by the Institution, as evidenced
by written documentation.
(v) is required by law or regulation to be disclosed. In the
event that information is required to be disclosed pursuant to subsection v, the
party required to make disclosure shall notify the other to allow that party to
assert whatever exclusions or exemptions may be available to it under such law
or regulation.
8. PUBLICATION RIGHTS. The Sponsor acknowledges that the Institution is
dedicated to free scholarly exchange and to public dissemination of the results
of their scholarly activities. The Principal Investigator and the Institution
shall retain the right to publish research results in pursuit of educational and
scientific purposes. However, the Institution expressly agrees that all drafts
of any publications or oral presentations, including without limitation
manuscripts, abstracts, posters, and visual works based on the Study or any
results of the Study shall be submitted to the Sponsor at least thirty (30) days
prior to the proposed submission of such drafts for publication or presentation.
Such publications and presentations shall not divulge any of the Sponsor's
Confidential Information without prior written approval of the Sponsor, and the
Institution shall promptly remove any Confidential Information identified and
requested by the Sponsor. If requested by the Sponsor, the Principal
Investigator and the Institution shall delay the submission of any publication
or presentation up to sixty (60) days from the date of the Sponsor's request for
such a delay to permit the preparation and filing of related patent
applications. in addition, the Sponsor shall have the right to require that any
publication or presentation concerning the work performed hereunder acknowledge
the Sponsor's support.
9. INVENTIONS. "Invention" shall mean any discovery, concept, or idea,
whether or not patentable, made during the conduct of the study, and arising
directly from the performance of the study, including but not limited to
processes, methods, software, tangible research products, formulas and
techniques, improvements thereto, and know-how related thereto.
Institution agrees that the Principal Investigator will promptly
disclose to its Intellectual Property Committee and to Sponsor any Inventions
made by the Institution and/or the Principal
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Investigator. It is agreed that all Inventions and any information with respect
thereto shall be subject to confidentiality obligations commensurate with those
set forth in Section 7 herein.
Any Inventions that originate solely with the Principal Investigator, or
any other Institution agent or employee associated with this study (jointly or
severally referred to as "Inventor") shall be the property of Institution. If
Inventor is a co-inventor with Sponsor, its agents or employees, Institution and
Sponsor shall jointly own the Invention. Any Inventions that originate solely
with any agent or employee of Sponsor shall be the property of Sponsor. To the
extent that Sponsor pays all patent expenses for an Invention, Institution does
hereby grant to Sponsor an exclusive option to negotiate an exclusive, worldwide
royalty-bearing license to any Invention in which Institution has an ownership
interest. Sponsor shall indicate its intention to exercise its option to license
by notifying Institution in writing within forty-five (45) days of each
Invention's disclosure to Sponsor. If Sponsor decides to exercise its option,
the terms shall be negotiated in good faith within one-hundred twenty (120) days
of the date the option is exercised, or within such time as the parties may
mutually agree in writing.
If negotiations between Sponsor and the Institution terminate and the
Institution thereafter negotiates a license agreement with a third party on
substantially better terms than those last offered to Sponsor, Sponsor shall be
given the first right to refuse such terms for a period of sixty (60) days from
the date of Sponsors receipt of a draft of such license agreement from
Institution.
10. INDEMNIFICATION BY SPONSOR. The Sponsor will indemnify, hold
harmless and defend the System, Institution, their Regents, officers, agents,
and employees (collectively the "Indemnitees") against all actions, suits,
claims, demands and prosecutions (hereinafter a "Claim") that may be brought or
instituted, and all judgments, damages, liabilities, costs and expenses
resulting therefrom, arising out of the activities to be carried out pursuant to
the obligations under this Agreement, including but not limited to the use by
Sponsor of the results obtained from the activities performed by Institution
under this Agreement, but only to the extent that any such Claim is not caused
by or the result of: (a) any negligence or willful act or omission of any
Indemnitees; or (b) failure to adhere to the terms of the protocol provided by
the Sponsor hereunder. The Sponsor's indemnification obligations under this
Section 10 only arise if: (i) the Institution notifies the Sponsor within (30)
thirty days after it becomes aware of a Claim; (ii) the Institution, subject to
the Statutory duties of the Texas Attorney General permits the Sponsor control
the defense and settlement, at the Sponsor's expense, of any such Claim; (iii)
the Institution and Principal Investigator fully cooperate with the Sponsor in
the defense of any such claim, and (iv) the Institution does not settle any such
Claim without the prior written approval and consent of the Sponsor.
11. INDEMNIFICATION BY INSTITUTION. Institution shall to the extent
authorized under the Constitution and laws of the State of Texas, indemnify and
hold Sponsor harmless from liability resulting from the negligent acts or
omissions of Institution, its agents or employees pertaining to the activities
to be carried out pursuant to the obligations of this Agreement; provided,
however, that Institution shall not hold Sponsor harmless from claims arising
out of the negligence or willful malfeasance of Sponsor, its officers, agents,
or employees, or any person or entity not subject to Institutions supervision or
control.
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12. LIABILITY INSURANCE. The Sponsor will maintain during the term of
this Agreement liability insurance with minimum limits of not less than
$1,000,000. As soon as practicable upon execution of this Agreement, the Sponsor
will deposit with the Institution certificates of insurance evidencing this
coverage. Such coverage may not be changed or terminated except upon at least
thirty (30) days prior written notice to the Institution. In addition, the
Sponsor will at all times comply with all statutory workers' compensation and
employers' liability requirements covering its employees with respect to
activities performed under this Agreement.
13. RELATIONSHIP OF THE PARTIES. The Institution and the Principal
Investigator shall both be deemed to be independent contractors for all purposes
and for all services to be provided under this Agreement, and neither the agent
nor the employee of the Sponsor. The Institution shall have no authority to make
any statements, representations or commitments of any kind, or to take any
action, which shall be binding upon the Sponsor, except as expressly provided
for in this Agreement or authorized in Writing by the Sponsor.
14. REPRESENTATIONS AND WARRANTIES OF INSTITUTION. Institution
represents that the Principal Investigator and all other investigators that may
perform services hereunder are its employees and shall abide by the terms of
this Agreement as if each were a party hereto.
15. WARRANTIES; LIMITATION OF LIABILITY. THE SPONSOR MAKES NO
WARRANTIES, EXPRESS OR IMPLIED, AS TO ANY PRODUCT OR OTHER MATERIALS OR
PROCESSES PROVIDED HEREUNDER. EXCEPT AS EXPRESSLY STATED HEREIN, THE SPONSOR
SHALL NOT BE LIABLE FOR ANY DIRECT, CONSEQUENTIAL, PUNITIVE, INDIRECT, OR OTHER
DAMAGES SUFFERED BY THE INSTITUTION OR THE PRINCIPAL INVESTIGATOR AS A RESULT OF
THE STUDY.
16. TERM. This Agreement shall be effective from the Effective Date of
this Agreement and shall expire thirty (30) days after receipt by Sponsor of the
final summary of work accomplished during the Study. This Agreement may be
terminated by either party upon fourteen (14) weeks written notice.
17. RETURN OF PRODUCT. Upon termination of this Agreement, the
Institution will return to the Sponsor all non-disposable Product, test kits,
and packaging materials as well as all copies of drawings, specifications,
manuals and other printed or reproduced material (including information stored
on machine-readable media) provided by the Sponsor to the Institution or the
Principal Investigator. The Sponsor may, at the Sponsor's option, request that
such materials be destroyed. All equipment purchased with funds under this
Agreement will become the property of Institution.
18. MISCELLANEOUS.
A. AMENDMENTS AND WAIVERS. Any term of this Agreement may be
amended or waived only with the written consent of the parties or their
respective successors and assigns. Any amendment or waiver effected in
accordance with this Section 18(a) shall be binding upon the parties and their
respective successors and assigns.
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B. NOTICE. Any notice required or Permitted by this Agreement
shall be in writing and shall be deemed sufficient upon receipt, when delivered
personally or by courier, overnight delivery service or confirmed facsimile, or
forty-eight (48) hours after being deposited in the regular mail as certified or
registered mail (airmail if sent internationally) with postage prepaid, if such
notice is addressed to the party to be notified at such party's address or
facsimile number as set forth below, or as subsequently modified by written
notice.
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INSTITUTION: SPONSOR:
University of Texas Northwest Bio therapeutics, Inc.
M.D. Xxxxxxxx Cancer Center 000 Xxxxxxxxx Xxxxx, Xxxxx 000
0000 Xxxxxxxx Xxxx., Xxx 000 Xxxxxxx, XX 00000
Xxxxxxx, Xxxxx 00000
ATTENTION: Xxxxx Xxxxxxx, C.P.A. ATTENTION: Xxxxxx X. Xxxxx
Manager, Grants & President and CEO
Contracts Accounting
If by FAX: (000) 000-0000 If by FAX: (000) 000-0000
If by express mail: same as address above If by express mail: same address
as above
C. ASSIGNMENT. The Institution agrees not to assign any of its
rights or obligations under this Agreement to any other party without first
obtaining the Sponsor's written approval. The terms and conditions of this
Agreement shall inure to the benefit of and be binding upon the respective
permitted successors and assigns of the parties. Nothing in this Agreement,
express or implied, is intended to confer upon any party other than the parties
hereto or their respective successors and assigns any rights, remedies,
obligations, or liabilities under or by reason of this Agreement, except as
expressly provided in this Agreement.
D. GOVERNING LAW; JURISDICTION. This Agreement shall be construed
in accordance with the laws of the State of Texas.
E. SEVERABILITY. If one or more provisions of this Agreement are
held to be unenforceable under applicable law, the parties agree to renegotiate
such provision in good faith, in order to maintain the economic position enjoyed
by each party as close as possible to that under the provision rendered
unenforceable. In the event that the parties cannot reach a mutually agreeable
and enforceable replacement for such provision, then (i) such provision shall be
excluded from this Agreement, (ii) the balance of the Agreement shall be
interpreted as if such provision were so excluded and (iii) the balance of the
Agreement shall be enforceable in accordance with its terms.
F. FORCE MAJEURE. Performance of this Agreement by each party
shall be pursued with due diligence in all requirements hereof, however, neither
party shall be liable to the other for any loss or damages for delay or for
nonperformance due to causes not reasonably within its control. The party
affected shall promptly notify the other in writing of the nature, cause, date
of commencement thereof, the anticipated extent of such delay.
G. ENTIRE AGREEMENT. This Agreement is the product of both of the
parties hereto, and constitutes the entire agreement between such parties
pertaining to the subject matter hereof, and merges all prior negotiations and
drafts of the parties with regard to the transactions contemplated herein. Any
and all other written or oral agreements existing between the parties hereto
regarding such transactions are expressly canceled.
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The parties hereto have caused this Agreement to be executed on their
behalf by their duly authorized representatives to he effective on the year and
date first above written.
NORTHWEST BIOTHERAPEUTICS, INC.
By: /s/ Xxxxxx X. Xxxxx
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Name: Xxxxxx X. Xxxxx
Title: President and Chief Executive
Officer
Date: 12-16-99
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THE UNIVERSITY OF TEXAS, M.D.
XXXXXXXX CANCER CENTER
By: /s/ Xxxxxxx X. Xxxxxxxx
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Name: Xxxxxxx X. Xxxxxxxx, M.D., M.B.A.
Title: Associate Vice President,
Research Administration
Date: 12-28-99
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I have read this agreement and understood my obligations hereunder:
/s/ Xxxxxxxx Xxxxxxxxxx Date: 12-20-99
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Xxxxxxxx Xxxxxxxxxx, M.D., Ph.D.
PRINCIPAL INVESTIGATOR,
STUDY CHAIRMAN
/s/ Xxxxxxxxxxx Xxxxxxxxxx Reviewed and Approved
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Xxxxxxxxxxx Xxxxxxxxxx, M.D.
Chairman, Department of Genitourinary
Medical Oncology
Date: 12-28-99
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/s/ Xxxxxx X. Xxxx
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Xxxxxx X. Xxxx, Xx., M.D.
Head, Division of Medicine
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EXHIBIT A
Northwest Biotherapeutics, Inc. Study Protocol No. DC1-HRPC
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EXHIBIT B
M.D. Xxxxxxxx Cancer Center Study Protocol No. ID99-333
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EXHIBIT C
Budget
Personnel Salary & Fringe $149,117
Equipment 2,453
Supplies 2,560
Patient Costs (Research Costs Only for 30 Patients) 71,669
Subtotal: Direct Costs 225,799
Indirect Costs 39,294
TOTAL DIRECT + INDIRECT COSTS 265,093
Payment
The Institution will require the Principal Investigator to agree to use
best efforts to complete the Study within the budgeted amount of eight thousand
eight hundred thirty-six Dollars and 43/00 ($8,836.43) per patient up to a
maximum of 30 patients, for a total estimated budget of two hundred sixty-five
thousand ninety-three Dollars ($265,093) (hereinafter referred to as the "Total
Estimated Budget") as itemized and set forth above.
Any expenditure for time and/or materials which is expected to increase
the total amount for the completed Study to be invoiced by the Institution to
Sponsor in excess of the Total Estimated Budget shall be approved in advance in
writing by Sponsor. The Budget is based on a single Leukapheresis per patient.
The Sponsor will pay for any additional Leukapheresis procedures and associated
tests required for Leukapheresis when the Sponsor and Principal Investigator
agree that additional Leukapheresis is required.
The Institution will invoice Sponsor on a calendar quarterly basis for
expenses for work under this Agreement. The initial payment of twenty-five
percent (25%) will be due within thirty (30) days of the signing of this
agreement by the Sponsor and the Institution. Checks payable to the Institution
shall be sent to:
The University of Texas
M.D. Xxxxxxxx Cancer Center
Attn: Manager, Grants and Contracts Accounting
X.X. Xxx 000000
Xxxxxxx, Xxxxx 00000
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EXHIBIT D
PAYMENT SCHEDULE
The Company will pay to the Institution a total of eight thousand eight hundred
thirty-six dollars and 43/00 ($8,836,43) for each patient who completes the
Protocol and for whom the Company receives all reports required by the Protocol
(the "Cost per Patient") up to a maximum of thirty (30) patients. The Company
will make an initial payment of sixty-six thousand two hundred seventy-three
dollars and 23/00 ($66,273.23) representing twenty-five percent (25%) of the
Cost per Patient (the "Initial Payment") derived from Exhibit B and payable
thirty (30) days after the execution of this Agreement. The Initial Payment will
be credited toward the first 25% of the Cost per Patient that becomes due and
payable by the Company. The Initial Payment will be refunded to the Company to
the extent, it any, by which the initial Payment exceeds the total Cost per
Patient that becomes due.
The Cost per Patient will become due as follows:
- 25% payable within 30 days of the Sponsor's and the Institution's execution
of this agreement;
- Up to an aggregate of 60% will be payable in quarterly payments due within
30 days of receipt of Institution's detailed invoices;
- And, the final balance within 30 days of Sponsor's receipt of Institution's
final report.
The amount payable by the Company will be pro-rated for any patient who fails to
complete the Protocol. IN ALL CASES, PATIENT EXPENSES ELIGIBLE FOR THIRD-PARTY
REIMBURSEMENT ARE THE RESPONSIBILITY OF THE INSTITUTION AND WILL NOT BE CHARGED
TO THE SPONSOR.
The Company will withhold the final fifteen per cent (15%) of the total Cost per
Patient until all Case Reports and the Clinical Trial summary report have been
delivered to the Company, and both the Company and the Institution's IRB have
been notified that the Clinical Trial has been completed.
Requests for payment must be in the form of a detailed invoice and submitted to
Northwest Biotherapeutics, Inc. Except for the Initial Payment, the Company will
not be obligated to make any payments until a detailed invoice has been
received. All amounts due will be payable within thirty (30) days of receipt of
the Institution's invoice.
Detailed Invoices shall be addressed to:
Xx. X.X. Xxxxxxx
Xx. Manager of Clinical and Medical Affairs
Northwest Biotherapeutics, Inc,
000 Xxxxxxxxx Xxxxx, Xxxxx 000
Xxxxxxx, Xxxxxxxxxx 00000
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