EXHIBIT 10.24
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
MASTER LABORATORY SERVICES AGREEMENT
This Master Laboratory Services Agreement ("Agreement"), when signed by
both parties, will set forth the terms and conditions between NORTHWEST
BIOTHERAPEUTICS, INC., a Delaware corporation with its principal offices located
at 00000 00xx Xxxxx XX, Xxxxx 000, Xxxxxxx, Xxxxxxxxxx 00000 ("Sponsor") and
QUINTILES LABORATORIES LIMITED, a North Carolina corporation with its principal
offices located at 0000 Xxxxxxxxx Xxxxxxx, Xxxxx 000, Xxxxxx, Xxxxxxx 00000
("QLAB"), under which QLAB agrees to provide laboratory services to Sponsor as
set forth below.
Sponsor and QLAB agree as follows:
1. SERVICES. QLAB shall provide study planning, consultation on laboratory
design, laboratory analysis, other laboratory services, and/or data management
services, as requested by Sponsor from time to time during the term of this
Agreement. The specific details of each assignment or task will be separately
negotiated and specified in writing on terms acceptable to the parties and
otherwise subject to the terms and conditions of this Agreement (each such
writing, a Confirmation of Central Laboratory Services ("CCLS")) in a document
substantially in the form of Appendix I to this Agreement.
2. PAYMENT OF FEES AND EXPENSES.
(a) Each CCLS shall contain a provisional services budget ("PSB") for
the payment of QLAB's services to be performed pursuant to such CCLS as well as
additional terms and conditions related to the PSB. Sponsor will pay QLAB in
accordance with each PSB. Sponsor shall reimburse QLAB for all reasonable and
necessary travel, lodging and other expenses incurred in the performance of its
services that have been approved in writing by Sponsor.
(b) Upon execution of a CCLS, Sponsor shall pay QLAB an amount equal to
* of the applicable PSB as a project initiation payment. QLAB will draw from
these funds in order to pay for services and related costs and expenses
consistent with the terms of this Agreement.
(c) QLAB will invoice Sponsor monthly or as separately agreed for
services rendered under any CCLS and Sponsor shall pay all amounts due within
thirty (30) days of receipt of QLAB's itemized invoices for work completed. Each
invoice will reflect QLAB's application of any amounts advanced by Sponsor. If
any portion of an invoice is disputed, then Sponsor shall pay the undisputed
amounts within 30 days of receipt of the invoice, and the parties shall use good
faith efforts to reconcile the disputed amounts as soon as practicable.
(d) Overdue payments shall accrue interest at the rate of thirteen
percent (13%) per annum, and payments overdue for more than ninety (90) days
shall accrue interest at the rate of eighteen percent (18%) per annum, (or the
maximum lesser amount permitted by law) plus reasonable attorney's fees and
costs incurred by QLAB in connection with the collection thereof.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
3. TERM. This Agreement shall commence on the date of execution and shall
continue until terminated as hereinafter provided by either party.
4. CONFIDENTIALITY.
(a) It is understood that during the term of this Agreement and each
CCLS, QLAB and its employees will be exposed to data and information, which is
confidential and proprietary to Sponsor. All such data and information ("Sponsor
Confidential Information") made available, disclosed or otherwise made known to
QLAB as a result of services under this Agreement or under any CCLS shall be
considered confidential and shall be considered the sole property of Sponsor.
All information regarding laboratory methods, laboratory pricing, and laboratory
management and all information regarding QLAB's operations, including but not
limited to QLAB Property (as defined in Section 5 below), disclosed by QLAB to
Sponsor in connection with this Agreement or any CCLS is proprietary,
confidential information belonging to QLAB (the "QLAB Confidential Information",
and together with the Sponsor Confidential Information, collectively referred to
as the "Confidential Information"). The Confidential Information shall be used
by the receiving party and its employees only for purposes of performing the
receiving party's obligations hereunder or under any CCLS. Each party agrees
that it will not reveal, publish or otherwise disclose the Confidential
Information of the other party to any third party without the prior written
consent of the disclosing party who may withhold such consent for any reason.
(b) The foregoing obligations shall not apply to Confidential
Information which:
(i) is or becomes generally available to the public other than as
a result of a disclosure by the receiving party;
(ii) becomes available to the receiving party on a non-confidential
basis from a source which is not prohibited from disclosing
such information by a legal, contractual or fiduciary
obligation to the disclosing party;
(iii) the receiving party develops independently of any disclosure
by the disclosing party;
(iv) was in the receiving party's possession or known to the
receiving party prior to its receipt from the disclosing
party, as shown by contemporaneous written evidence; or
(v) is required by law to be disclosed.
(c) This obligation of confidentiality and non-disclosure shall remain
in effect for a period of ten years after the termination of this Agreement.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
5. PROPERTY OWNERSHIP.
(a) All data and information necessary for QLAB to conduct project
assignments will be forwarded by Sponsor to QLAB, and all such information
received from Sponsor shall remain the property of Sponsor.
(b) All data and information generated or derived by QLAB as the result
of services performed by QLAB under this Agreement shall be and remain the
exclusive property of Sponsor. Any inventions that may evolve from the data and
information described above or as the result of services performed by QLAB under
this Agreement ("Inventions") shall belong to Sponsor, and QLAB agrees to assign
all of its rights, title and interest in and to any Inventions and/or related
patents, effective upon their creation or conception to Sponsor. In addition,
QLAB:
i. shall assist Sponsor, at Sponsor's request and expense, during
and after the term of this Agreement, to evidence, transfer,
vest, perfect and enforce Sponsor's intellectual property
rights in the Inventions, and will execute any and all
instruments and perform all acts reasonably necessary or
desirable in order to establish, evidence, transfer, perfect,
enforce, vest or confirm in Sponsor the entire right, title
and interest in such Inventions, and also to execute any
instruments necessary or desirable in connection with any
continuations, renewals, or re-issues thereof or in the
conduct of any related proceedings, litigation or other
enforcement actions; provided that Sponsor's expenses
hereunder shall include reasonable compensation to QLAB for
its time spent in connection with enforcement actions or
proceedings; and
ii. shall promptly and fully disclose to Sponsor all Inventions
made, conceived or reduced to practice during the term of this
Agreement, and will promptly (in no event more than five
business days) deliver them to Sponsor upon request and in any
event upon the expiration or termination of this Agreement or
its term, other than termination due to Sponsor's material
breach of the Agreement; and
iii. agrees that all Inventions created as a result of services
performed under this Agreement are specifically ordered or
commissioned by Sponsor, and to the extent such Inventions
qualify as "works made for hire" under applicable copyright
law, they are hereby agreed to be "works made for hire." To
the extent such Inventions are not "works made for hire" under
applicable copyright law, QLAB agrees to assign (or cause to
be assigned) and does hereby assign fully to Sponsor the
exclusive ownership of the copyright in all such Inventions
and all rights comprised therein, along with ownership of and
title to all physical embodiments (in whatever media) of the
works, which shall vest in Sponsor as the works are fixed in
any tangible medium of expression.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
(c) Notwithstanding the foregoing, Sponsor acknowledges that QLAB
possesses certain inventions, processes, know-how, trade secrets, improvements,
other intellectual properties and other assets, including but not limited to
laboratory analyses, analytical and laboratory methods, processes, approaches,
procedures and techniques, technical expertise and conceptual expertise in area
of laboratory services, procedure manuals, personnel data, financial
information, computer technical expertise, and software, which have been
independently developed by QLAB and which relate to its business or operations
(collectively "QLAB Property"). Sponsor and QLAB agree that any QLAB Property or
improvements thereto which are used, improved, modified or developed by QLAB
under or during the term of this Agreement or any CCLS are the sole and
exclusive property of QLAB.
(d) At the completion of the services by QLAB, all materials and other
data owned by Sponsor shall either be: (i) delivered to Sponsor in such form as
is then currently in the possession of QLAB, subject to the payment obligations
set forth in Section 2 herein; (ii) retained by QLAB for Sponsor for a period of
two (2) years; or, (iii) disposed of, at the direction and written request of
Sponsor. Sponsor shall pay the costs associated with any of the above options.
Each party, however, reserves the right to retain, at its own cost and subject
to the confidentiality provisions herein, one copy of all documents and
materials relating to the services, to be used solely to satisfy regulatory
requirements or to resolve disputes regarding the services.
6. REGULATORY COMPLIANCE; INSPECTIONS.
(a) In carrying out its responsibilities under this Agreement and each
CCLS, QLAB agrees to conduct its services in compliance with all applicable
laws, rules and regulations, including but not limited to the U.S. Food, Drug
and Cosmetic Act and the regulations promulgated pursuant thereto, and with the
standard of care customary in the central laboratory industry.
(b) Sponsor warrants that neither any assignment or task requested by
Sponsor nor the conduct thereof as provided in this Agreement or in any CCLS
shall violate any applicable law or regulation. Sponsor shall notify QLAB
promptly in writing of any FDA or other governmental inspection or inquiry
concerning any services that have been rendered or are being rendered by QLAB,
or any study or project to which such services relate.
(c) Neither QLAB nor any of QLAB's employees rendering services pursuant
to this Agreement has been debarred pursuant to Section 306 of the Federal Food,
Drug, and Cosmetic Act, as amended, and QLAB will not knowingly employ any
person or entity that has been so debarred to perform services under this
Agreement or any CCLS. QLAB shall notify Sponsor immediately upon the
commencement of any such proceeding concerning QLAB or any such employee.
(d) If any governmental or regulatory authority conducts or gives notice
to QLAB of its intent to conduct an inspection at QLAB's facilities or take any
other regulatory action with respect to any study or services provided under
this Agreement, QLAB will promptly give Sponsor notice
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
thereof, including all information pertinent thereto, and, where reasonably
practicable, QLAB will notify Sponsor prior to complying with such a demand or
request. Sponsor, however, acknowledges that it may not direct the manner in
which QLAB fulfills its obligations to permit inspection by governmental
entities.
(e) During the term of this Agreement and each CCLS, QLAB will permit
Sponsor's representative(s) (unless such representatives are competitors of
QLAB) to examine the work performed hereunder and the specific facilities at
which the work is conducted during regular business hours upon reasonable
advance notice and in a reasonable manner to determine that the project
assignment is being conducted in accordance with the applicable CCLS and that
the facilities are adequate; provided, however, that all information, other than
Sponsor Confidential Information, disclosed or revealed to or ascertained by
Sponsor in connection with any such examination shall be deemed to constitute
QLAB Confidential Information for purposes of this Agreement. Unless the costs
of governmental audits related to this Agreement or CCLS or Sponsor audits are
specifically included in the PSB, Sponsor shall reimburse QLAB for its time and
expenses associated with such audits and investigations.
7. CONFLICT OF AGREEMENTS. QLAB represents to Sponsor that QLAB is not a
party to any agreement which would prevent QLAB from fulfilling its obligations
under this Agreement, and that during the term of this Agreement, QLAB will not
enter into an agreement to provide services which would prevent QLAB from
providing the services contemplated to be provided by QLAB under this Agreement
or any CCLS.
8. INDEMNIFICATION.
(a) Sponsor shall defend, indemnify and hold harmless QLAB, its
affiliates and its and their respective directors, officers, employees and
agents (each, an "Indemnified Party") from and against any and all losses,
claims, actions, damages, liabilities, costs and expenses, (including reasonable
attorney's fees and court costs) (collectively, "Losses"), joint or several,
resulting or arising from any third-party claims, actions, proceedings,
investigations or litigation relating to or arising from or in connection with
this Agreement or any CCLS or the services contemplated herein (including,
without limitation, any Losses arising from or in connection with any study,
test, product or potential product to which this Agreement or any CCLS relates),
except to the extent such Losses are determined to have resulted solely from
negligence or intentional misconduct of the Indemnified Party seeking indemnity
hereunder.
(b) QLAB shall: (i) give Sponsor prompt notice of any such claim or law
suit (including a copy thereof served upon QLAB); (ii) cooperate with Sponsor
and its legal representatives in the investigation of any matter the subject of
indemnification, and (iii) not unreasonably withhold its approval of the
settlement of any such claim, liability or action by Sponsor that is the subject
of this Indemnification provision.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
(c) Subject to Section 9 below, QLAB will defend, indemnify and hold
Sponsor harmless from and against all Losses arising from any breach of QLAB's
warranties, covenants or obligations under this Agreement or otherwise arising
out of or in connection with QLAB's negligent acts or negligent omissions.
Amounts finally determined to be owing under this paragraph may be deducted from
any payments owed by Sponsor to QLAB under this Agreement.
9. LIMITATION OF LIABILITY. Neither QLAB nor its affiliates nor any of its or
their respective directors, officers, employees or agents shall have any
liability of any type (including, but not limited to, contract, negligence and
tort liability) for any special, incidental, indirect or consequential damages,
including, but not limited to the loss of opportunity, loss of use, or loss of
revenue or profit in connection with or arising out of this Agreement, any CCLS,
or the services performed by QLAB hereunder, even if such damages may have been
foreseeable to QLAB. In addition, in no event shall the collective, aggregate
liability of QLAB and its affiliates and its and their respective directors,
officers, employees and agents under this Agreement or any CCLS exceed the
amount of fees actually received by QLAB from Sponsor pursuant to this Agreement
for the assignment or task from which such liability arose.
10. DISCLOSURE OF HAZARDS. Sponsor shall provide QLAB with all information
available to it regarding known or potential hazards associated with the use of
any substances supplied to QLAB by Sponsor and Sponsor shall comply with all
current legislation and regulations concerning the shipment of substances by
land, sea or air.
11. PUBLICATION. Project results may not be published or referred to, in whole
or in part, without the prior written consent of Sponsor. Neither party may use
the other party's name in connection with any publication or promotion without
the other party's prior, written consent, which consent will not unreasonably be
delayed or withheld.
12. TERMINATION.
(a) This Agreement or any CCLS may be terminated with or without cause
by Sponsor or by QLAB at any time during the term of this Agreement on ninety
(90) days prior written notice to QLAB or Sponsor, as appropriate.
(b) Either party may terminate this Agreement or any CCLS for material
breach upon thirty (30) days written notice specifying the nature of the breach,
if such breach has not been substantially cured within the thirty (30) day
period. In the event that QLAB in good faith, reasonably determines, in its sole
discretion, that its continued performance of the services contemplated by a
CCLS would constitute a potential or actual violation of regulatory or
scientific standards of integrity, QLAB may terminate this Agreement or the
applicable CCLS by giving written notice stating the effective date (which may
be less than thirty days from the notice date) of such termination.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
(c) Termination of this Agreement shall constitute termination of all
CCLS's hereunder. Termination of a CCLS shall constitute a termination of such
CCLS only and shall not affect this Agreement or any other CCLSs outstanding
hereunder. Any written termination notice shall identify each specific CCLS that
is being terminated.
(d) In the event this Agreement is terminated, Sponsor shall pay to
QLAB: (i) any fees for services rendered then due and owing to QLAB because of
any performance of QLAB's obligations hereunder and all expenses reasonably
incurred in performing those services; (ii) all actual costs (including time
spent by QLAB personnel, which shall be billed at QLAB standard rates) to
complete activities associated with the termination and close out of projects;
and (iii) all kit destruction costs as noted in each CCLS. If payments in a
terminated CCLS are milestone-based, but that milestone has not yet been
completed, Sponsor will pay QLAB's standard fees for actual work performed
toward that milestone up to the date of termination. Upon the termination of
this Agreement, QLAB shall deliver to Sponsor all data and materials provided by
Sponsor to QLAB for the conduct of services under this Agreement.
(e) Termination of this Agreement or any CCLS hereunder shall not
constitute a release or waiver of any right or remedy available to either party
in connection herewith or therewith.
13. INDEPENDENT CONTRACTOR RELATIONSHIP. Notwithstanding any provision herein
to the contrary, the parties hereto are independent contractors, and nothing
contained in this Agreement or in any CCLS shall be construed to place them in
the relationship of partners, principal and agent, employer and employee, or
joint venturers. Each party agrees that it shall have no power or right to bind
or obligate the other, and neither party shall hold itself out as having such
authority.
14. INSURANCE. Each Party shall have and maintain such types and amounts of
liability insurance as is normal and customary in the industry generally for
parties similarly situated, and shall upon request provide the other Party with
a copy of its policies of insurance in that regard, along with any amendments
and revisions hereto.
15. FORCE MAJEURE AND RELATED MATTERS. QLAB shall not be liable or responsible
to Sponsor nor be deemed to have defaulted under or breached this Agreement or
any CCLS for or in respect of errors, delays or other consequences arising from
Sponsor's failure to provide documents, materials, information or cooperation
required by QLAB in order to perform properly and timely QLAB's obligations
hereunder or thereunder. Sponsor acknowledges that, if it materially delays or
suspends performance of the services, then the personnel and/or resources
originally allocated to the project may be re-allocated, and QLAB will not be
responsible for delays due to required re-staffing or re-allocation of
resources. Any delay or hindrance in the performance of any of the duties or
obligations of either party hereto (except the payment of money owed) shall not
be considered a breach of this Agreement and the time required for performance
shall be extended for a period equal to the period of such delay, provided that
such delay has been caused by or is the result of any labor
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
disputes, including strikes, lockouts, job actions or boycotts; inability to
procure materials or services; riots; insurrection; embargoes; war; acts of God;
acts of the public enemy; inclement weather; fires; explosions; floods or other
natural disasters; or other reasons or causes beyond the reasonable control of
the party seeking to perform.
16. NOTICES AND DELIVERIES. Any notice required or permitted to be given by
either party hereunder shall be in writing and shall be deemed given on the date
received if delivered personally or by nationally recognized overnight delivery
service or three days after the date postmarked if sent by registered or
certified U.S. mail, return receipt requested, postage prepaid to the following
addresses:
If to QLAB: Quintiles Laboratories Limited
0000 Xxxxxxxxx Xxxxxxx, Xxxxx 000
Xxxxxx, Xxxxxxx 00000
Attn: S. Xxx Xxxxxxxxxx
Chief Operating Officer
If to Sponsor: Northwest Biotherapeutics, Inc.
00000 00xx Xxxxx XX, Xxxxx 000
Xxxxxxx, XX 00000
Attn: Director of Clinical Operations
The expense and risk of loss for all deliveries, shipments, and mailings shall
be born by Sponsor. QLAB disclaims any liability for loss or damage occurring
during shipment, delivery or mailing, except to the extent that such loss or
damage is caused by the negligence or intentional misconduct of QLAB.
17. MISCELLANEOUS.
(a) GOVERNING LAW. This Agreement and each CCLS shall be construed,
interpreted in accordance with and enforced under the laws of the State of
Washington, without regard to the conflict of laws provisions thereof. If any
one or more provisions of this Agreement or any CCLS shall be found to be
illegal or unenforceable in any respect, it is the intent of the parties that
such provisions be replaced, reformed or narrowed so that their original
business purpose can be accomplished to the extent permitted by law, the
validity, legality and enforceability of the remaining provisions shall not in
any way be affected or impaired thereby.
(b) SURVIVAL. The obligations of the parties contained in Sections 4, 5,
6, 8, 9 and 11 shall survive the termination of this Agreement.
(c) ENTIRE AGREEMENT; AMENDMENTS. This Agreement, together with each
CCLS, contains the entire understanding of the parties with respect to the
subject matter herein, and
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
supersedes all previous agreements (oral and written), negotiations and
discussions. The parties may modify or amend the provisions hereof only by an
instrument in writing duly executed by the parties.
(d) BINDING AGREEMENTS AND ASSIGNMENT. This Agreement shall be binding
upon and inure to the benefit of Sponsor and QLAB and their respective
successors and permitted assigns. Neither this Agreement nor any of either
party's rights hereunder may be assigned or otherwise transferred by either
party without the prior written consent of the other.
(e) WAIVER. No waiver by either party of any breach of any provision of
this Agreement or any CCLS shall constitute a waiver of any other or subsequent
breach.
(f) HEADINGS. The descriptive headings of the sections of this Agreement
are inserted for convenience only and shall not control or affect the meaning or
construction of any provision hereof.
(g) INCORPORATION BY REFERENCE. All exhibits attached hereto shall be
deemed to be incorporated herein. In case of any conflict between this Agreement
and any such attachment or any CCLS, the terms of this Agreement shall prevail
over the attachment or CCLS.
(h) For all CCLS's in which QLAB will earn fees or incur expenses in
excess of one million U.S. Dollars in a currency differing from the invoice and
payment currency, a foreign currency exchange provision will be included in the
CCLS.
(i) Any controversy or claim arising out of or relating to this
Agreement or the breach thereof shall be settled by arbitration administered by
the American Arbitration Association ("AAA") under its Commercial Arbitration
Rules, and judgment on the award rendered by the arbitrator shall be binding and
may be entered in any court having jurisdiction thereof. Such arbitration shall
be filed and conducted at the office of the AAA closest to QLAB if initiated by
Sponsor or, nearest to Sponsor if initiated by QLAB, and shall be conducted in
English by one arbitrator mutually acceptable to the parties selected in
accordance with AAA Rules.
IN WITNESS WHEREOF, this Agreement has been executed by the parties hereto
through their duly authorized officers and is effective as of the last date set
forth below.
QUINTILES LABORATORIES LIMITED NORTHWEST BIOTHERAPEUTICS, INC.
By: /s/ S. XXX XXXXXXXXXX By: /s/ XXXXXX X. XXXXX
------------------------------------ -----------------------------------
S. Xxx Xxxxxxxxxx Xxxxxx X. Xxxxx
Title: Chief Operating Officer Title: Chairman, President and CEO
Quintiles Laboratories Worldwide
Date: November 14, 2001 Date: November 21, 2001
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
APPENDIX I-1
CONFIRMATION OF
CENTRAL LABORATORY SERVICES
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL DC3-HRPC
NOVEMBER 14, 2001
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
This Confirmation of Central Laboratory Services specifies the terms and
conditions upon which Quintiles Laboratories ("QLAB") will provide analytical
and data management services for the clinical trial described herein. QLAB, or
its agents, make no other commitments or warranties, either expressed or
implied, concerning the scope of services to be provided during the course of
this agreement. The Sponsor and its agents recognize and affirm that the
liability for any breach by QLAB shall be limited to the amount of fees paid to
QLAB by Northwest Biotherapeutics, Inc. or its agents before and during the
course of Northwest Biotherapeutics, Inc. Protocol DC3-HRPC.
PROTOCOL IMPLEMENTATION AND SUPPORT
A.1 Projected Time Period and Scope of Services
Confirmation of Central Laboratory Services Date: November 14, 2001
Protocol Number: DC3-HRPC
Project Initiation: September 2001
Investigator Sites: 25 - United States
Enrolled Patients: 495
Average Patients per Site: 19-20
A.2 Protocol Specific Scope of Work
QLAB, in conjunction with The Sponsor, will complete a protocol specific Scope
of Work. The Scope of Work will define all of the protocol and procedural
parameters necessary for database construction kit specification & design,
customized requisitions & reports, and the investigator instruction manual.
A.3 Visit Specific Kits
QLAB will provide to each investigator site all materials necessary for
collection and transport of specimens to be tested at QLAB in accordance with
industry standards. These materials will include visit-specific laboratory
requisitions and kits designed to meet the needs of this clinical trial. All
laboratory requisitions, collection materials and mailers will be pre-labeled
with a unique bar-coded accession number. The accession number will be used
throughout the study to ensure accurate tracking, collation, and reporting of
patient laboratory data.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
A.4 Investigator Training
QLAB will provide a protocol-specific instruction manual to each investigator
and training to the study coordinators in all laboratory procedures and services
pertaining to this clinical trial at the Investigator meeting. Items to be
covered will include, but will not be necessarily limited to, proper specimen
collection and processing, on-site archival of frozen specimens, and shipping of
samples under conditions to maximize analyte stability. The Sponsor or its
designated representative will provide QLAB with investigator telephone,
facsimile and site number. QLAB will send site verification forms to check
delivery addresses for supplies and laboratory reports as well as 24-hour, 7-day
telephone numbers for communication of telephone and panic alert test results.
QLAB will be eligible for reimbursement of all production and distribution costs
of investigator meeting materials as well as any reasonable travel-related
expenses incurred therein. All Materials will be printed in English. Documents
printed in languages other than English will result in additional fees.
A.5 Expedited Specimen Transport
QLAB will be responsible for arranging for express shipping with a courier who
provides a system by which clinical trial specimens can be tracked during
shipment. The risk of loss during shipment, however, shall be born by The
Sponsor, and Quintiles disclaims any liability for loss or damage occurring
during shipment, except to the extent that such loss or damage is caused by the
negligence or intentional misconduct of QLAB.
In the continental United States, ambient specimens can be shipped Monday
through Saturday on the day of collection. Ambient specimen shipments from sites
in Canada will be limited to Monday through Friday on the day of collection,
with the exception of remote locations. Ambient specimen shipments from sites in
Alaska and Hawaii will be limited to Monday through Thursday on the day of
collection. Frozen shipments from sites in the continental United States and
Canada will be limited to Monday through Thursday, and Monday through Wednesday
for sites in Alaska and Hawaii.
A.6 Ancillary Shipping Procedures
Sunday or holiday shipments may result in fees in excess of the visit fee.
Ancillary shipping fees will be subject to prior approval by The Sponsor unless
QLAB's Laboratory Director deems it necessary to act immediately in order to
ensure that specimens are received within the established limits of analyte
stability.
A.7 Dry Ice Services
QLAB does not provide dry ice services. However, QLAB can assist in the
coordination of dry ice services in certain regions on an optional basis only.
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* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
A.8 Patient Identification
From customized visit specific laboratory requisitions, QLAB will collect and
report patient demographic data as required by The Sponsor's protocols and
procedures and based on QLAB's capabilities.
DATA GENERATION AND TRANSMITTAL
B.1 Laboratory Data Reporting
Laboratory reports of test results will be sent to the investigators via
facsimile on the day testing is completed, followed by weekly hard copy reports.
Laboratory report formats will be determined during the protocol planning and
implementation phase.
B.2 Notification of Alerts
QLAB will contact investigators as defined in the Scope of Work with Telephone
High, Telephone Low, Panic High, Panic Low and Exclusion Alerts. QLAB will
contact The Sponsor or its designated representative with Panic Highs and Lows
and for all flags if the investigator cannot be reached.
B.3 Blinding
Blinding of selected laboratory results is available as an optional service from
QLAB. If The Sponsor determines that there is a requirement for blinding of
results in this clinical trial, such requirements will be defined in the Scope
of Work.
B.4 Electronic Data Transmission
QLAB will transfer clinical trial data in a pre-determined format, media and
schedule directly from our facility to The Sponsor's data management facility or
designated representative location.
B.5 Status Report
QLAB will provide The Sponsor or its designated representative with status
reports throughout the conduct of this trial summarizing the number of patients
tested to date by visit for each investigator site. The frequency and mode of
distribution of the status report are defined in the Scope of Work.
B.6 Data Retention
QLAB will maintain on-line all laboratory data compiled from this clinical trial
for the term of the clinical trial plus 18 months. Thereafter, all laboratory
data will be archived onto compact disc
-13-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
media for a period of ten years. At the end of that ten-year period, QLAB will
forward electronic records to The Sponsor or retain for an additional fee,
according to The Sponsor's written instructions.
B.7 Confidentiality
QLAB will maintain the confidentiality of information related to the conduct and
results of this clinical trial as outlined in QLAB's internal policies, or under
the provisions of a Confidentiality Agreement to be executed with The Sponsor,
or under the provisions of any Master Services Agreement or Master Laboratory
Services Agreement that applies to this Confirmation of Laboratory Services.
B.8 QNET Software Product
If Sponsor requests the use of QNET in the Scope of Work, QLAB will provide
Sponsor or its designated party with the services of the QNET software product
according to the terms and conditions of the QNET SOFTWARE LICENSE AGREEMENT
agreed to under separate signature of both QLAB and Sponsor. QLAB will be
eligible for reimbursement of all pre-approved travel-related expenses incurred
with the installation of QNET at the Sponsor designated location(s) as well as
pre-approved travel-related expenses incurred as part of any required QNET
support.
ANALYTICAL SERVICES
C.1 Laboratory Events Schedule
The schedule for analytical and related laboratory services for The Sponsor's
Protocol DC3-HRPC is outlined as Exhibit A.
C.2 Test Groups
Analytical services referenced in the Laboratory Events Schedule for Protocol
DC3-HRPC are outlined as Exhibit B.
C.3 Analytical Standards and Certification
QLAB will maintain all state and federal licenses required to perform diagnostic
testing on interstate specimens. QLAB documents all in-house quality control and
quality assurance programs and will make available applicable results from
inter-laboratory proficiency programs conducted by the College of American
Pathologists or similar accrediting organizations during central laboratory
audits (see section C.16 Central Laboratory Audits).
-14-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
C.4 Analytical Methodology Comparability
In order to provide consistency of results throughout the clinical trial
program, QLAB will maintain the same test methodology and procedures utilized
for the first laboratory-testing visit. The Sponsor may elect to adopt new and
improved technology or revised procedures whenever QLAB makes them available.
The Sponsor recognizes that circumstances beyond the control of QLAB can arise
which would preclude the use of the same testing methodology throughout the
clinical trial. Should this situation arise, QLAB will confer with The Sponsor
prior to the selection of an alternative methodology.
C.5 Specimen Stability
Analytical services will not be performed on specimens for which the elapsed
time from collection to analysis exceeds established limits of analyte
stability. QLAB also reserves the right to cancel testing on specimens whose
physical or chemical condition may jeopardize result integrity.
C.6 Test Priority Specified by Sponsor
Testing of quantity not sufficient (QNS) specimens can be performed in a
pre-determined and prioritized order established by The Sponsor. All QNS testing
will be conducted within the limits of QLAB's analytical capabilities.
C.7 Reference Ranges and Reporting Units
Reference ranges and units will be those established by QLAB's Quality Assurance
Group as those, which are appropriate and available for the test methodologies
being used in this clinical trial. QLAB reserves the right to periodically amend
reference ranges as changes in instrumentation, reagent formulation,
international standards, governmental recommendations, and testing methodologies
are adopted throughout the clinical laboratory industry. However, no changes
will be implemented without the explicit knowledge and consent of The Sponsor.
C.8 Exclusion Criteria
One exclusion value for each analyte and at specified visits may be selected by
The Sponsor. All test results for a given analyte will be compared to this
value. Results will be flagged as EX on the QLAB laboratory report.
C.9 High and Low Flags
Test results will be compared to sex stratified ranges and will be flagged as
High or Low if the result violates the established range.
-15-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
C.10 Telephone Alert and Panic Alert Values
Telephone and Panic Alert values will be those levels selected by the Sponsor
where such levels are appropriate and available from QLAB. QLAB reserves the
right to not implement a Panic Alert level that is inconsistent with generally
accepted clinical laboratory standards. QLAB's Laboratory Director will discuss
the setting of Panic Alert levels with the Sponsor as appropriate.
C.11 Delta Flags
Delta flags will be reported for those patients whose laboratory values differ
by a specified percentage relative to the laboratory visit established by The
Sponsor as the baseline. Delta changes will be reported as +D or -D if the
checked value has increased or decreased relative to the reference visit.
C.12 Specimen Retention
All specimens will be retained for a period of up to 7 days after reporting and
will be made available for repeat testing if the elapsed time since specimen
collection falls within the established limits of stability. Repeat testing will
be performed at no additional charge if it is required due to the negligent acts
or omissions of QLAB.
C.13 Specimen Management
QLAB will be responsible for monitoring and maintaining the temperature and
other environmental conditions for frozen specimens which are being stored for
an interim period prior to batch testing or shipping to another analysis
facility. Storage times and conditions will be specified by The Sponsor in
advance of the clinical trial commencement.
C.14 Specimen Storage
Long term specimen storage is a standard service offering of QLAB. Long term
storage is defined as being a period greater than seven (7) days. If The Sponsor
requests this service from QLAB, additional fees will be included in the
Provisional Services Budget.
C.15 Central Laboratory Auditing
The Sponsor shall have the ability, upon reasonable notice to QLAB, to visit
QLAB and examine all systems, documents and other materials related to the
study. If The Sponsor audits QLAB, the parties shall cooperate and work in good
faith to resolve any unsatisfactory audit findings. In addition, QLAB shall
reasonably cooperate with and shall allow the Food and Drug Administration (FDA)
and other governmental agencies to visit QLAB and to examine all systems,
documents and other materials related to the study.
-16-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
FEES AND BILLING
D.1 Scheduled Visit Fees
Scheduled visit fees which include analytical testing by visit and reporting
along with database configuration, maintenance and transfer, project management,
and transportation costs are included in Exhibit C.
D.2 Kit Construction Fees
Kit construction fees which include the cost of visit specific collection kits
and materials, as well as shippers, are included in the Provisional Services
Budget. Sponsor will be invoiced for these costs at the time they are shipped to
the investigator sites.
D.3 Transportation Fees
All transportation fees in the Provisional Services Budget are estimates.
Transportation will be handled as a direct pass through cost to The Sponsor on
the monthly invoice. Quintiles Laboratories applies a kit transportation
management fee to each kit for the administrative cost of managing the
transportation of supplies to the sites and the movement of samples to QLAB
and/or a sponsor designated location.
D.4 Unscheduled Visit Fees and Optional Test Fees
The fee for Services rendered by Quintiles Laboratories which relate to
unscheduled visits is set forth in Exhibit C and shall be paid in accordance
with the terms set forth therein. Any visits not listed in Exhibit C are
considered unscheduled visits, fees for which are to be paid pursuant to the
terms of Exhibit C. Unscheduled visit fees are not included in the Provisional
Services Budget and, therefore, are not subject to the Initiation Fee.
Unscheduled visit fees will be invoiced during the course of the study when they
occur. Fees for optional tests are set forth in the Provisional Services Budget
and relate to laboratory procedures required by the Protocol but performed only
on selected patients under certain conditions, and will be invoiced as
appropriate during the course of the study. (EXAMPLE: OPTIONAL TEST - SERUM
PREGNANCY).
D.5 Expenses
QLAB shall be reimbursed by The Sponsor for all-reasonable and necessary travel
and lodging expenses incurred in the performance of services provided herein
which have been pre-approved by The Sponsor. Additionally, investigator site
special requests for supplies that are not included in the bulk supply kit or
other special requests shall be approved by and reimbursed by The Sponsor.
Payment for such services shall be made to QLAB within thirty (30) days of
receipt by The Sponsor
-17-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
of invoices or other evidence of such expenditures. Sponsor/CRO provided
investigator information (name, address, phone and fax number) will be used when
shipping study collection materials to investigators, as well as the
construction of investigator data base information. If the Sponsor/CRO provided
investigator information is incorrect and QLAB is assessed a transportation
penalty fee for non-deliverable packages, QLAB will invoice The Sponsor for
assessed penalty fees plus a database change fee of $ * .
D.6 Terms of Project Initiation Invoicing
After award of the project by The Sponsor, QLAB will invoice a project
initiation fee of * of the value of the estimated Provisional Services Budget.
The initiation fee will be credited back to The Sponsor against the final
invoice for the project.
D.7 Invoices and Billing
Laboratory services will be invoiced based on the receipt of specimens. An
invoice for all visit specific specimens received during the month plus any
expenses incurred will be issued to The Sponsor the following month. If
requested, QLAB can provide a detailed report listing the invoiced visits by
investigator name, accession number, date and visit name. Payment is due within
thirty (30) days of the invoice date.
Please remit payments to:
Quintiles Laboratories Limited
X.X. Xxx 000000
Xxxxxxxxx, XX 00000-0000
D.8 Test and Fee Cancellation
If some or all testing for a particular visit cannot be completed due to
circumstances beyond the control of QLAB, all valid test results will be
reported and the total visit fee will remain in effect. Examples of
circumstances which can result in billable test cancellations would be: (1)
failure to include a specimen required to complete testing for the visit, (2)
specimen handling prior to courier pickup which does not meet written guidelines
established by the laboratory and (3) provision of a QNS specimen for which all
requested testing cannot be completed.
D.9 Clinical Trial Reconciliation
When The Sponsor informs QLAB in writing of the completion or cancellation of
the clinical trial, reconciliation will be conducted. This accounting will
reconcile any outstanding clinical trial-specific project initiation expenses,
scheduled or unscheduled visit fees and unsalvageable specimen collection
materials at the investigator sites. A credit or debit invoice will be issued.
-18-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
D.10 Cancellation of the Clinical Trial
Upon receiving written notification of early cancellation of the clinical trial,
QLAB will provide The Sponsor with an accounting of all clinical trial-specific
project initiation expenses, scheduled and unscheduled visit fees and
unsalvageable specimen collection materials at the investigator sites. QLAB will
charge * of the PSB as a cancellation fee. If the value of efforts extended and
supplies shipped exceeds * of the total PSB, an invoice will be presented for
those fees.
D.11 Approval of Fee and Period in Force
The provisional fee schedule will expire 60 days from the date of this
Confirmation of Central Laboratory Services. Upon receiving verbal approval from
The Sponsor, QLAB will implement project initiation activities as outlined
previously in Sections A.2 and D.6. If there is a substantive change in the
expected number of investigators, number or schedule of visits, testing
requirements, anticipated commencement date, length of project or overall
protocol specific database design, QLAB will revise the Provisional Services
Budget to reflect the increase or decrease in the scope of work. Otherwise, the
fees will remain in effect for 12 months from the date study kits were first
forwarded to investigator sites. QLAB fee schedule will be subject to review on
an annual basis and will be increased for the next 12 month period based upon
the average percent change in the US Consumer Price Index over the preceding 12
month period. In the unforeseen event of governmentally mandated changes or
transportation industry regulation changes which require significant changes in
the conduct of the clinical laboratory industry, QLAB will contact The Sponsor
if there will be any cost impact on the study in progress. Additionally, if QLAB
courier fees increase 10% or more, or a fuel surcharge is imposed on QLAB for
courier services, The Sponsor will be notified immediately of the cost impact on
the study in progress.
D.12 Currency Exchange
The currency to be used to invoice and for payment is set forth in this
Provisional Services Budget attached hereto as Exhibit C (the "PSB"). If QLAB is
to perform services whereby it earns fees or incurs expenses that exceed * U.S.
dollars in a currency(ies) differing from the invoice and payment currency
(hereafter, "foreign currency(ies)"), the initial foreign currency exchange
rates used as a basis for calculating the PSB (the "PSB Rates") shall be stated
in the PSB. For each monthly invoice prepared by QLAB, QLAB will obtain the
applicable foreign currency exchange spot rates published in the Wall Street
Journal {or the Financial Times for European-based Projects} on the last
business Friday of the month to which the invoice relates (the "Current Rates").
FOR MILESTONE-BASED INVOICES, THE CURRENT RATES SHALL BE THE AVERAGE OF SUCH
FOREIGN CURRENCY EXCHANGE SPOT RATES FOR THE LAST BUSINESS FRIDAY OF EACH MONTH
BETWEEN MILESTONE INVOICES. If the Current Rates differ from the PSB Rates, a
currency adjustment will be calculated. The currency adjustment will be
calculated as the difference between the amount to be invoiced at the Current
Rates and the amount to be invoiced at the PSB Rates. If the amount to be
invoiced at the Current Rates exceeds or is less than the amount to be invoiced
at the PSB Rates, QLAB will reflect
-19-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
a debit or credit adjustment, as appropriate to the monthly invoice. The PSB
will state for each currency its percentage of the total fees (and expenses, if
applicable), after its conversion into the invoice and payment currency, which
will be applied to all invoices. If a currency referenced within the PSB is
replaced by the Euro or otherwise ceases to become legal tender, the applicable
replacement currency will be substituted for such currency for purposes of this
provision at an established conversion rate.
-20-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
ACKNOWLEDGED, ACCEPTED AND AGREED TO BY:
/s/ S. XXX XXXXXXXXXX November 14, 2001
------------------------------------ --------------------------
S. Xxx Xxxxxxxxxx Date
Chief Operating Officer
Quintiles Laboratories Worldwide
Authorized Representative of Northwest Biotherapeutics, Inc.:
Xxxxx XxXxxx
--------------------------------------------------------------------------------
(Type or print name)
Director of Clinical Operations
--------------------------------------------------------------------------------
(Type or print title)
/s/ XXXXX XXXXXX 11/21/01
------------------------------------ --------------------------
Signature Date
-21-
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
LABORATORY EVENTS SCHEDULE EXHIBIT A
VERSION 09 START DATE: MID SEPTEMBER 2001
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL: DC3-HRPC - DOUBLE-BLIND, PLACEBO-CONTROLLED
INDICATION: PROSTATE CANCER PROJECT CODE: AP1215
ENROLLMENT PERIOD: * MONTHS PATIENT DURATION: 36 MONTHS
CENTERS: 25 - UNITED STATES
------------------------------------------------------------------------------------------------------------------------------------
SCREEN BASELINE TIME WK WK WK WK WK WK WK WK WK 18 24 30 36 RETEST
NO. OF PATIENTS* 0 4 8 12 16 20 24 38 42 52 MO MO MO MO AS
* * * * * * * * * * * * * NEEDED
------------------------------------------------------------------------------------------------------------------------------------
CHEMISTRY W/ 16 CONSTITUENTS x x x x x x x x x x x x x -
HAEMATOLOGY W/ DIFFERENTIAL &
PLATELET COUNT x x x x x x x x x x x x x -
URINALYSIS W/ MICROSCOPIC x x -
TESTOSTERONE, TOTAL x x -
PROSTATE SURFACE ANTIGEN (PSA) x x x x x x x x x x x -
PROSTATIC ACID PHOSPHATASE (PAP) x x x x x x x x x x x -
ANTI-NUCLEAR ANTIBODIES TITER (XXX) x x x x x x x x x x x x x -
ANTI-NUCLEAR ANTIBODIES PATTERN (XXX) # # # # # # # # # # # # # -
XXXXXXXXXX FACTOR x x x x x x x x x x x x x -
HEPATITIS B SURFACE ANTIGEN (HBSAG) x -
HEPATITIS B CORE TOTAL ANTIBODY
(ANTI-HBC) x -
HIV 1 / 2 EIA SCREEN x -
ANTI-HEPATITIS C ANTIBODY (ANTI-HCV) x -
RAPID PLASMA XXXXXX (RPR) x -
HTLV-I / II IGG, AB x -
HIV-1 FREE ANTIGEN x -
SPECIMEN COLLECTION & TESTING MATERIALS:
ERYTHROCYTE SEDIMENTATION RATE (ESR)(a) x x x x x x x x x x x x x
SPECIMEN COLLECTION MATERIALS: * x x x x x x x x x x x x x
SPECIMEN COLLECTION MATERIALS: * x x x x x x x x x x x x x
(10) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7)
KEY: x Scheduled - Unscheduled # If needed
(a) Quintiles Laboratories will provide the centers with the testing
kits/materials for consistency in methodology of on-site analysis
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
LABORATORY EVENTS SCHEDULE EXHIBIT A
VERSION 09 START DATE: MID SEPTEMBER 2001
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL: DC3-HRPC - OPEN LABEL
INDICATION: PROSTATE CANCER PROJECT CODE: AP1239
ENROLLMENT PERIOD: * MONTHS PATIENT DURATION: 36 MONTHS
CENTERS: 25 - UNITED STATES
-----------------------------------------------------------------------------------------------------------------------------------
BASELINE TIME WK WK WK WK WK WK WK WK WK 18 24 30 36 RETEST
NO. OF PATIENTS* 0 4 8 12 16 20 24 38 42 52 MO MO MO MO AS
* * * * * * * * * * * * * NEEDED
-----------------------------------------------------------------------------------------------------------------------------------
CHEMISTRY W/ 16 CONSTITUENTS x x x x x x x x x x x x -
HAEMATOLOGY W/ DIFFERENTIAL & PLATELET COUNT x x x x x x x x x x x x -
URINALYSIS W/ MICROSCOPIC x -
TESTOSTERONE, TOTAL x -
PROSTATE SURFACE ANTIGEN (PSA) x x x x x x x x x x -
PROSTATIC ACID PHOSPHATASE (PAP) x x x x x x x x x x -
ANTI-NUCLEAR ANTIBODIES TITER (XXX) x x x x x x x x x x x x -
ANTI-NUCLEAR ANTIBODIES XXXXXXX (XXX) # # # # # # # # # # # # -
RHEUMATOID FACTOR x x x x x x x x x x x x -
SPECIMEN COLLECTION & TESTING MATERIALS:
ERYTHROCYTE SEDIMENTATION RATE (ESR)(a) x x x x x x x x x x x x
SPECIMEN COLLECTION MATERIALS: * x x x x x x x x x x x x x
SPECIMEN COLLECTION MATERIALS: * x x x x x x x x x x x x x
(10) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7) (7)
KEY: x Scheduled - Unscheduled # If needed
(a) Quintiles Laboratories will provide the centers with the testing
kits/materials for consistency in methodology of on-site analysis.
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
EXHIBIT B
LABORATORY REQUIREMENTS
VERSION 09
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL: DC3-HRPC
INDICATION: PROSTATE CANCER
CHEMISTRY URINALYSIS(1)
Sodium PH
Potassium Specific Gravity
Chloride Glucose
Bicarbonate Protein
BUN Ketones
Creatinine Blood
Magnesium Microscopic
Calcium METHOD: BAYER MULTISTIX/MANUAL MICROSCOPY
Phosphorus
Glucose SPECIAL CHEMISTRY
ALT (SGPT) Testosterone, Total(2a)
AST (SGOT) METHOD: BAYER CHEMILUMINESCENCE
Total Bilirubin Prostate Specific Antigen (PSA)(2a)
Albumin METHOD: XXXXXX XXXX
Alkaline Phosphatase Prostatic Acid Phosphatase (PAP)(2b)
LDH METHOD: ICMA
METHOD: ROCHE BMD
IMMUNOLOGY
HAEMATOLOGY(1) Anti-Nuclear Antibodies Titer (XXX)(2a)
Haemoglobin Anti-Nuclear Antibodies Pattern (XXX)(2a)
Haematocrit METHOD: IFA
MCV Rheumatoid Factor(2a)
MCH METHOD: ROCHE TINAQUANT
MCHC
RBC
WBC
Platelet Count
RBC Morphology
Differential
RDW
METHOD: XXXXXXX/XXXXXXX/MANUAL MICROSCOPY
PLEASE NOTE: Quintiles Laboratories will provide the centers with all the
materials necessary for specimen collection, temporary storage and overnight
shipping of samples. Services assume that all samples will ship ambient on the
day of collection, unless otherwise noted.
(1) Quintiles Laboratories assumes standard test panels. Customization of
testing may result in budget changes.
(2) The centers will collect the specimens and store at - 20(degree)C or colder.
On the day of collection at the Screen Visit and at the Baseline Visit and
monthly thereafter, the centers will ship the frozen samples on dry ice (to be
provided BY the centers) to Quintiles Laboratories.
(2a) Upon receipt, Quintiles Laboratories will analyze the samples and
issue a laboratory report.
(2b) Upon receipt Quintiles Laboratories will repackage the samples and
forward to Specialty Laboratories for analysis. The results will be
entered into the Quintiles Laboratories protocol specific database and
reports will be issued to the centers.
* AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
EXHIBIT B
LABORATORY REQUIREMENTS
VERSION 09
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL: DC3-HRPC
INDICATION: PROSTATE CANCER
VIROLOGY SPECIMEN COLLECTION & TESTING MATERIALS
Hepatitis B Surface Antigen (HBsAg) Erythrocyte Sedimentation Rate (ESR)(4)
Hepatitis B Core Total Antibody (Anti-HBc)
HIV 1/2 EIA Screen SPECIMEN COLLECTION MATERIALS(5)
Hepatitis C Antibody (Anti-HCV) *
METHOD: XXXXXX EIA
Rapid Plasma Xxxxxx (RPR)
METHOD: XXXXXX-XXXXXXX MACRO-VUE
HTLV-I / II IgG, Ab(3)
METHOD: EIA
HIV-1 Free Antigen(3)
METHOD: EIA/IB
(3) Upon receipt Quintiles Laboratories will forward the ambient samples to
Specialty Laboratories for analysis. The results will be entered into the
Quintiles Laboratories protocol specific database and reports will be issued to
the centers.
(4) Quintiles laboratories will provide the centers with the testing
kits/materials for consistency in methodology of on-site analysis.
(5) *
*AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
PROVISIONAL SERVICES BUDGET - LINE ITEM - NORTH AMERICA EXHIBIT C
VERSION: 09
NORTHWEST BIOTHERAPEUTICS, INC.
PROTOCOL: DC3-HRPC - DOUBLE-BLINDED, PLACEBO-CONTROLLED
INDICATION: PROSTATE CANCER
-----------------------------------------------------------------------------------------------------------------------
NO. OF EXTENDED
SERVICE OR TEST DESCRIPTION PATIENT VISITS* FEE* FEE*
-----------------------------------------------------------------------------------------------------------------------
ADMINISTRATIVE / DATABASE
SET UP & PROJECT MANAGEMENT (fees based on a project
duration of * for enrollment; 36 months patient duration.
Extensions to the duration of the project may result in additional fees). *
DATABASE DEVELOPMENT *
DATABASE TRANSMISSIONS & ROUTINE MAINTENANCE * * *
ANALYTICAL TESTING
CHEMISTRY W/ 16 CONSTITUENTS * * *
HAEMATOLOGY W/ DIFFERENTIAL & PLATELET COUNT * * *
URINALYSIS W/ MICROSCOPIC * * *
TESTOSTERONE, TOTAL * * *
PROSTATE SURFACE ANTIGEN (PSA) * * *
PROSTATIC ACID PHOSPHATASE (PAP): SPECIALTY LAB * * *
ANTI-NUCLEAR ANTIBODIES TITER (XXX) * * *
ANTI-NUCLEAR ANTIBODIES PATTERN (XXX) * * *
RHEUMATOID FACTOR * * *
HEPATITIS SCREEN PANEL (HBsAg and ANTI-HCV) * * *
HEPATITIS B CORE TOTAL ANTIBODY (ANTI-Hbc) * * *
HIV 1/2 EIA SCREEN * * *
RAPID PLASMA XXXXXX (RPR) * * *
HTLV-I/II IgG, Ab: SPECIALTY LAB * * *
HIV-I FREE ANTIGEN: SPECIALTY LAB * * *
REPORTING
FAX REPORT TO INVESTIGATOR - UNITED STATES DAILY * * *
FAX REPORT TO INVESTIGATOR - UNITED STATES MONTHLY * * *
FAX REPORT TO INVESTIGATOR - SPECIALTY LAB REPORT * * *
QNET(TM) LABORATORY REPORTING SOFTWARE * * *
KIT CONSTRUCTION & SUPPLIES
KIT TRANSPORTATION MANAGEMENT FEE - UNITED STATES * * *
AMBIENT KITS * * *
*AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
* * * *
* * * *
NON-INFECTIOUS FROZEN SHIPPER * * *
ERYTHROCYTE SEDIMENTATION RATE (ESR) KITS * * *
TRANSPORTATION - UNITED STATES
BULK DISTRIBUTION - AMBIENT QKITS * * *
* * * *
* * * *
BULK DISTRIBUTION - NON-INFECTIOUS FROZEN SHIPPER * * *
INBOUND - AMBIENT QKITS * * *
* * * *
INBOUND - NON-INFECTIOUS FROZEN SHIPPER * * *
TOTAL PROVISIONAL SERVICES BUDGET $1,305,179.01
------------------------------------------------------------------------------------------------------------------------
NO. OF PATIENT EXTENDED
DESCRIPTION VISITS* FEE* FEE*
------------------------------------------------------------------------------------------------------------------------
ADMINISTRATIVE / DATABASE
Total for services outlined on line item budget *
VISIT FEES -- UNITED STATES (INCLUDES ANALYTICAL AND REPORTING)
SCREEN VISIT * * *
BASELINE VISIT * * *
TIME 0 VISIT, WEEKS 12, 20, 38, MONTHS 18, 24, 30 AND 36 VISITS * * *
WEEKS 4 AND 8 VISITS * * *
WEEK 52 VISIT * * *
RETEST VISIT * * *
KIT SUPPLY VISIT FEES -- UNITED STATES (INCLUDES KIT SUPPLIES
AND KIT TRANSPORTATION MANAGEMENT FEE)
SCREEN, BASELINE, TIME 0, WEEKS 4, 8, 12, 20, 38, 52,
MONTHS 18, 24, 30 and 36 VISITS KIT * * *
* * * *
* * * *
NON-INFECTIOUS FROZEN SHIPPER * * *
RETEST VISIT KIT * * *
*AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
TRANSPORTATION ESTIMATE FOR NORTH AMERICA (TOTAL FROM
SERVICES OUTLINED ON THE LINE ITEM BUDGET) *
PROVISIONAL SERVICES BUDGET $1,305,179.0
----------------------------------------------------------------------------------------------------------------------
NO. OF PATIENT EXTENDED
SERVICE OR TEST DESCRIPTION VISITS* FEE* FEE*
----------------------------------------------------------------------------------------------------------------------
ADMINISTRATIVE / DATABASE
SET UP & PROJECT MANAGEMENT (fees based on a project
duration of * for enrollment; 36 months patient duration. *
Extensions to the duration of the project may result in additional fees.
DATABASE DEVELOPMENT *
ANALYTICAL TESTING
CHEMISTRY W/ 16 CONSTITUENTS * * *
HAEMATOLOGY W/ DIFFERENTIAL & PLATELET COUNT * * *
URINALYSIS W/ MICROSCOPIC * * *
TESTOSTERONE, TOTAL * * *
PROSTATE SURFACE ANTIGEN (PSA) * * *
PROSTATIC ACID PHOSPHATASE (PAP): Specialty Lab * * *
ANTI-NUCLEAR ANTIBODIES TITER (XXX) * * *
ANTI-NUCLEAR ANTIBODIES PATTERN (XXX) * * *
RHEUMATOID FACTOR * * *
REPORTING
FAX REPORT TO INVESTIGATOR -- UNITED STATES DAILY * * *
FAX REPORT TO INVESTIGATOR -- UNITED STATES WEEKLY * * *
QNET(TM) LABORATORY REPORTING SOFTWARE * * *
KIT CONSTRUCTION & SUPPLIES
KIT TRANSPORTATION MANAGEMENT FEE -- UNITED STATES * * *
AMBIENT QKITS * * *
* * * *
* * * *
NON-INFECTIOUS FROZEN SHIPPER * * *
ERYTHROCYTE SEDIMENTATION RATE (ESR) KITS * * *
TRANSPORTATION -- UNITED STATES
BULK DISTRIBUTION -- AMBIENT QKITS * * *
*AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 7, 2001
INFORMATION HAS BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT
AND HAS BEEN FILED SEPARATELY WITH THE SEC.
* * * *
* * * *
BULK DISTRIBUTION -- NON-INFECTIOUS FROZEN SHIPPER * * *
INBOUND -- AMBIENT QKITS * * *
* * * *
INBOUND -- NON-INFECTIOUS FROZEN SHIPPER * * *
TOTAL PROVISIONAL SERVICES BUDGET $315,644.95
------------------------------------------------------------------------------------------------------------------------
NO. OF PATIENT EXTENDED
DESCRIPTION VISITS* FEE* FEE*
------------------------------------------------------------------------------------------------------------------------
ADMINISTRATIVE / DATABASE
Total for services outlined on line item budge *
VISIT FEES -- UNITED STATES (INCLUDES ANALYTICAL AND REPORTING)
BASELINE VISIT * * *
TIME 0 VISIT, WEEKS 12, 20, 38, MONTHS 18, 24, 30 AND 36 VISITS * * *
WEEKS 4 AND 8 VISITS * * *
WEEK 52 VISIT * * *
RETEST VISIT * * *
KIT SUPPLY VISIT FEES -- UNITED STATES (INCLUDES KIT SUPPLIES AND
KIT TRANSPORTATION MANAGEMENT FEE)
SCREEN, BASELINE, TIME 0, WEEKS 4, 8, 12, 20, 38, 52, MONTHS 18,
24, 30 AND 36 VISITS KIT * * *
* * * *
* * * *
NON-INFECTIOUS FROZEN SHIPPER * * *
RETEST VISIT KIT * * *
TRANSPORTATION ESTIMATE FOR NORTH AMERICA (TOTAL FROM SERVICES
OUTLINED ON THE LINE ITEM BUDGET) *
PROVISIONAL SERVICES BUDGET $315,644.95
