PROJECT CONTRACT
This Project Contract dated 01 June 2007 (" Effective Date" ) is issued pursuant to the Master Agreement dated 12 December 2003 between Genta, Inc. (" GENTA" ) and ICON Clinical Research, L.P. (" ICON" ). Except as modified by this Project Contract, the terms and conditions of the Agreement are incorporated herein by reference and shall govern the performance of the parties' duties under this Project Contract. Capitalized terms used herein and not otherwise defined are used as defined in the Master Agreement.
1.
Protocol . The Study to be performed is entitled " A Multicenter, Randomized, Double-Blind Study of Dacarbazine With or Without Genasenseae in Chemotherapy-Naefve Subjects With Advanced Melanoma and Low LDH, Protocol Number GM307" and is set forth in the Protocol attached as Exhibit A and incorporated herein by reference. For purposes of this Project Contract, the Study Drug for the Study is defined as Genasenseae.
2.
ICON Proposal . The services to be performed by ICON for the Study (" Services" ) and associated costs are set forth in the proposal attached as Exhibit B and incorporated herein by reference.
3.
Payment Schedule . In consideration for ICON' s Services under this Project Contract, GENTA agrees to pay ICON in accordance with the payment schedule set forth in the attached Exhibit C and incorporated herein by reference. The total amount payable by GENTA to ICON under this Project Contract for direct labor costs shall in no way exceed * without prior written consent of both parties. All pass-through costs are estimated.
4.
Transfer of Obligations . Pursuant to 21 CFR a7312.52, GENTA hereby transfers to ICON and ICON hereby assumes all the obligations of GENTA as sponsor of the Study as set forth in Exhibit D attached and incorporated herein by reference and included on Form FDA 1571, Section 13. GENTA shall retain the right to assume any of the duties delegated to ICON at any time and the Services and Exhibit C shall be adjusted accordingly.
5.
Key Personnel . ICON agrees to use its best efforts to maintain continuity in ICON Personnel assigned to perform the Services, which key personnel are named in the attached Exhibit E.
6.
Term . This Project Contract shall begin as of the Effective Date and shall be completed by March 31, 2011, when all of the Services are fully performed in accordance with Exhibit B, unless terminated earlier pursuant to Paragraph 3.3 of the Master Agreement.
1
7.
Notices . Notices relating to this Project Contract shall be delivered in accordance with the Master Agreement and addressed as follows:
If to GENTA:
John Carbine
Director of Finance
Genta Incorporated
200 Connell Drive
Berkeley Heights, NJ 07922
Phone: 908-286-5977
Email: Carbine@genta.com
If to ICON:
Rose Bonner
Contract Analyst
212 Church Road
North Wales, PA 19454
Phone: 215-616-3589
FAX: 215-616-2727
Email: bonnerr@iconus.com
8.
Invoices and Payments . All ICON invoices should be forwarded to GENTA as follows:
Genta Accounts Payable
200 Connell Drive
Berkeley Heights, NJ 07922
PHONE: 908-286-5799
FAX: 908-464-9353
All payments should be forwarded to ICON pursuant to Section 4.5 of the Master Agreement as follows. Payments shall be in the form of a check drawn on a U.S. bank, payable to ICON Clinical Research, L.P. and mailed to:
ICON Clinical Research, L.P.
Attn.: Dave Peters, Vice President of Finance
P.O. Box 82-8268
Philadelphia, PA 19182-8268
Tax I.D. Number: 52-2133696
9.
Exhibits . The Exhibits attached hereto form an integral part of this Project Contract and are hereby incorporated by reference.
2
10.
Entire Agreement . With respect to the Services performed under this Project Contract, this Project Contract, including the attached Exhibits, and the Master Agreement contain the entire agreement of the parties. Any modifications to this Project Contract must be in writing and signed by the parties.
IN WITNESS WHEREOF, the parties hereto have executed this Project Contract as of the dates stated below.
ICON CLINICAL RESEARCH, L.P.
SPONSOR NAME
By:
By:
David Peters
Loretta M. Itri
Vice President, Finance
President, Pharmaceutical Development and Chief Medical Officer
Date:
Date:
3
Exhibit A
Protocol
Study/Protocol Number: GM307
Protocol Title:
A Multicenter, Randomized, Double-Blind Study of Dacarbazine With or Without Genasenseae in Chemotherapy-Naefve Subjects With Advanced Melanoma and Low LDH
Version Number and Date: version number 3, dated 27 July 2007
The above referenced protocol has previously been provided to ICON, and is incorporated herein.
4
Exhibit C
Payment Schedule
Direct Fees
ICON shall invoice Genta for direct fees in accordance with the following milestone based schedule.
Milestone
Payment
Percentage
Estimated Month
*
$250,000
*
Jun-07
*
$250,000
*
Jul-07
*
$350,000
*
Aug-07
*
$500,000
*
Sep-07
*
$774,831
*
Oct-07
*
$750,000
*
Oct-07
*
$1,197,070
*
Jan-08
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Total
*
100%
IVRS Fees
If IVRS system development is placed on hold by Genta for * or more, additional costs may be incurred to resume activities.
If enrollment is delayed after system go live, * of the monthly fee may be assessed for telephone and system maintenance.
5
The monthly fee will be assessed until IVRS and/or IWRS is no longer required. A minimum number of months will be billed (* of total number of months proposed) if all patients complete early (Prior to * of months proposed).
Monthly maintenance costs are based on Genta having adequate drug supply to allow the automated drug management system to run with no manual manipulation or interference. The monthly maintenance fee includes up to two manual shipments each month. Each additional manual shipment may be charged on a time & materials basis.
Pass-through Costs
Genta shall provide an upfront payment of * of the budget for all pass-through costs upon execution of this Project Contract. Additionally, each month ICON shall submit to Genta an invoice describing the pass-through costs incurred during a particular month and Genta shall pay all invoiced amounts within * days of receipt of such invoice. At the end of these Services, any excess funds held by ICON shall be returned to Genta.
All pass-through costs are estimated for budgetary purposes. Genta shall be invoiced for actual costs incurred.
6
Exhibit D
Transfer of Obligations
GENTA, as Sponsor of the Protocol / Project Contract, hereby transfers responsibilities for Clinical Trial Management, Medical and Safety Support, Data Management, and IVRS as outlined in Exhibit B, and ICON Clinical Research, L.P. hereby assumes such obligations, in accordance with 21 C.F.R. section 312.52.
7
Exhibit E
Key Personnel
NAME
TITLE
CONTACT DETAILS
ICON Clinical Research, L.P.
Maria Hermon
Global Clinical Project Manager
Phone: 512-295-5443 E-mail: HermonM@iconus.com
Brendan Kromer
EU Clinical Project Manager
Phone: +44(0) 1865-891-108 E-mail: KromerB@iconuk.com
Daniela Zlpp
ROW Clinical Project Manager
Phone: +61-2-9859-3934 E-mail: ZippD@iconger.com
Tom Williams
US Medical Affairs
Phone: 215-618-3250 E-mail: WilliamsT@iconus.com
Zuzana Georgen
EU Medical Affairs
Phone: +49-6103-904-1562 E-mail: GeorgenZ@iconger.com
Luke Chung
ROW Medical Affairs
Phone: +65-6895-8242 E-mail: ChungL@iconsing.com
Michelle O' Connell
Data Management Project Manager
Phone: 302-533-3027 E-mail: OconnellM@iconus.com
Ashley Threinen
IVRS Project Manager
Phone: 281-295-4836 E-mail: ThreinenA@iconus.com
Debra Nichols
Senior Director, Business Development
Phone: 401-667-0465 E-mail: NicholsD@iconus.com
Rose Bonner
Contract Analyst
Phone: 215-616-3589 E-mail: BonnerR@iconus.com
Genta, Inc.
Neilda Baron
Medical Director, Drug Safety & Surveillance/Medical Info
Phone: 908-219-3140 E-mail: baron@genta.com
Sharon Burke
Clinical Data Coordinator
Phone: 908-219-3108 E-mail: Burke@genta.com
John Carbine
Director of Finance
Phone: 908-286-5977 E-mail: Carbine@genta.com
Anila Cornet
Director of Quality Assurance
Phone: 908-286-6488 E-mail: Cornet@genta.com
Thierry Cousin
Clinical Project Physician EU
Phone: E-mail: CousinT@genta.com
8
Wendy Curran
Director of Clinical Operations
Phone: 908-286-3997 E-mail: CurranW@genta.com
Donna Eccleston
Clinical Data Coordinator
Phone: 908-219-3147 E-mail: Eccleston@genta.com
Janet Ehlert
Sr. Director, Medical Writing & Communication
Phone: 908-288-5922 E-mail: Ehlert@genta.com
Raymond Feeks
Pharmacovigilence
Phone: 908-288-5995 E-mail: Feeks@genta.com
Erard Gilles
Sr. Medical Director EU
Phone: 908-288-3974 E-mail: Gilles@genta.com
Robin McCabe
Clinical Trial Manager, Regions EU
Phone: 908-286-6452 E-mail: McCabe@genta.com
Bharat Mehta
VP Manufacturing Operations
Phone: 908-286-5952 E-mail: Mehta@genta.com
Steve Novick
Sr. Medical Director US
Phone: 908-286-5972 E-mail: Novick@genta.com
Bonnie Pappacena
Sr. Director of Quality Assurance
Phone: 908-286-5949 E-mail: Pappacena@genta.com
Jill Powers
Sr. Director of Regulatory Affairs
Phone: 908-286-3986 E-mail: Powers@genta.com
Anila Qureshi
Clinical Trial Manager, Regions US, Canada, Australia
Phone: 908-286-6456 E-mail: Qureshi@genta.com
Deborah Sollod
Pharmacovigilence
Phone: 908-219-3110 E-mail: Sollod@genta.com
Ed Spindler
Director of Project Management & Planning
Phone: 908-219-3122 E-mail: Spindler@genta.com
Christine Szkwarko
Sr. Director, Supply Chain
Phone: 908-286-5958 E-mail: Szkwarko@genta.com
Rafael Varona
Clinical Project Physician EU
Phone: E-mail: VaronaR@genta.com
Jane Wu
Sr. Director of Data Management & Biostatistics
Phone: 908-286-5933 E-mail: Wu@genta.com
9
Exhibit B
A revised Proposal for ICON Services in Support of a
Phase III Study Entitled
A Multicenter, Randomized, Double-Blind Study of Dacarbazine With or Without Genasenseae in Chemotherapy-Naefve Subjects With Advanced
Melanoma and Low LDH
Protocol: GM307
Prepared for:
John Carbine Director of Finance Genta Incorporated 200 Connell Drive Berkeley Heights, NJ 07922 Tel: 908-286-5977 Email: Carbine@genta.com
Prepared by:
ICON Clinical Research 212 Church Road North Wales, PA 19454 www.iconclinical.com
Questions to:
Debra Nichols Senior Director, Business Development Tel: (401) 667-0465 Email: NicholsD@iconus.com
Date:
24 October 2007 Version 4.0
10
Table of Contents
Cost Summary
12
Country / Site Distribution for a 16.5-Month Recruitment Period
13
Project Team
14
Study Timeline
17
Appendix I ICON Fees and Expenses
18
Appendix II Responsibilities Staff Allocation
25
Appendix III Responsibilities and Specifications
33
Responsibilities
33
Specifications
38
Appendix IV Specification Detail
43
Clinical Operations
44
Medical and Safety Monitoring
47
Data Management Oracle ClinicalTM
49
IVRS
57
11
Cost Summary
A summary of ICON professional fees and pass-through costs is presented below. A detailed cost estimate has been provided in Appendix I. The provided estimate was developed based upon the information provided by Genta as reflected in the Project Specifications section.
Project Cost Category
US
EU
ROW
Clinical Operations
*
*
*
Medical Affairs
*
*
*
Data Management
*
Interactive Voice Response System (IVRS)
*
ICONet
*
Subtotal Total Direct Fees
*
*
*
Estimated Pass-Through Costs*
*
*
*
Total Study Budget
*
*
*
______________ *
Investigator fees have not been included in this proposal.
12
Country / Site Distribution for a 16.5-Month Recruitment Period
The following is the site and country distribution as of July 31, 2007:
Table 1: 130 sites enrolling patients over a 16.5 month recruitment period
Country
No. of Sites
Patients screened
Patients Enrolled
Patients Completed
United States
21
105
79
79
UK
7
30
23
23
France
15
80
60
60
Germany
18
90
68
68
Austria
5
25
19
19
Italy
4
20
15
15
Czech Republic
1
5
4
4
Switzerland
1
5
4
4
Sweden
1
5
4
4
Spain
5
25
19
19
Australia
3
15
11
11
Canada
2
10
8
8
Grand Total
83
415
314
314
13
Project Team
ICON' s philosophy is to become an extension of Genta' s study team to facilitate seamless study conduct and communication. To achieve this goal, our proposed project team is based on the parameters supplied in Genta' s RFP as well as our own review. The proposed structure of our project team reflects the elements necessary to ensure a timely conclusion of this project. Curricula vitae (CVs) of proposed ICON project team members are provided below.
Global Therapeutic Advisor
Andreas Dreps, PhD, is ICON' s Global Therapeutic Lead for Oncology and is responsible for overseeing all oncology projects throughout their duration. He is based in ICON' s Langen Germany office and is Director of Oncology Research in Europe. During his 14 years of pharmaceutical industry experience, Dr. Dreps worked on the development of several chemotherapy agents (Taxolae, Taxotereae, and Camptoae), several molecular targeting agents such as monoclonal antibodies targeting the EGF-R (Erbituxae, EMD 72.000), an angiogenesis inhibitor (Cilengitide) and tumor vaccines (Theratopeae, BLP-25, and BEC-2). Andreas has an excellent understanding of the competitive environment with regard to other ongoing clinical trials targeting a similar patient population. Utilizing his exceptional oncology experience (especially during the site selection process) will be a distinct advantage in identifying the most qualified sites and keeping the timelines as short as possible.
US Project Manager
Maria Hermon is the US Project Manager for this Genta trial. Maria has been with ICON for four years and she has over 15 years of experience working in the clinical research industry. She has successfully managed numerous studies ranging from Phase I to Phase IV. Maria has experience managing studies in multiple therapeutic areas including oncology. Other therapeutic area experience includes cardiovascular, endocrine/ metabolic, gastrointestinal, infectious disease, medical device, musculoskeletal, neurology, ophthalmology, respiratory, skin and soft tissue, transplant and urology. Maria' s oncology experience along with her excellent project management skills will enable her to successfully manage this Genta study.
EU Clinical Project Manager
ICON proposes Brendan Kromer, Ph.D. based in our Marlow, UK office to manage clinical activities in Europe. Brendan brings extensive oncology trial experience, including the monitor, coordination and management of international phase II and III trials in solid and non-solid oncology indications. Brendon has also recently completed the management of a global, cardiovascular morbidity trial extending across 10,873 enrolled patients in 16 countries. In total, Brendon brings over 8 years of clinical research industry experience, including over 6 years of project management. His educational credentials include a Bachelor of Science (Hons) 2.1 in Pharmacology as well as a Ph.D. in Cardiovascular Pharmacology from the Imperial College, London. His career experience and medical expertise will provide assured management of services in Europe.
ROW Project Manager Australia & New Zealand
Daniela Venusta Zipp is the Australian & New Zealand Project Manager . Daniela has over 5 years of clinical research industry experience. Daniela was recently a Clinical Project Manager on a Breast Cancer study and has Non-Small Cell Lung Cancer monitoring
14
experience. Daniela' s experience in oncology makes her an excellent choice to lead this important Genta trial. Daniela is also fluent in German, English, Italian, and has basic Spanish skills, which will be an asset to this study.
US Medical Monitor
Thomas Williams, MD is the US Medical Monitor for this study. Dr. Williams is the Senior Director of the Oncology Division and is based in Austin, Texas. He is board certified in Hematology and Oncology and has been with ICON since 2002. Prior to joining ICON, Dr. Williams was Director of Medical Affairs at ILEX Oncology for seven years. He has more than 37 years of experience in clinical research, with 23 years of experience in academia. He has authored or co-authored 85 publications and 22 presentations. His areas of clinical expertise include cancer, bone marrow transplantation, hemophilia, and sickle cell anemia. Dr. Williams also has 16 years of industry experience and has participated in the clinical development of more than 68 investigational agents and biologics, including NDA submissions for four therapeutic agents for leukemia. He has participated in the development of clofarabine, vincristine, fuanazole, Elliott' s B Solution, methotrexate, thioguanine, mercaptopurine, Piritrexim, daunorubicin, azacitidine, dibromodulcitol, L-asparaginase, Erwinia asparaginase, homoharringtonine, deoxycoformycin, amsacrine, mitoxantrone, adriamycin, cytarabine, trans-retinoic acid, busulfan for injection, cyclophosmade, and CAMPATH-1H. Dr. Williams' postgraduate training was in Hematology-Oncology at the University of Virginia and in Bone Marrow Transplantation at the Johns Hopkins Medical School. He holds an M.D. degree from the University of Texas Southwestern Medical School. His career has centered on oncology and hematologic disorders, making him the perfect choice to provide the caliber of medical oversight and expertise that this Genta study requires.
EU Medical Monitor
The EU Medical Monitor is Zuzana Goergen, MD, a Clinical Research Physician based in our office in Langen, Germany. Dr. Goergen recently joined ICON and is a board certified Specialist in Dermatology (Germany). She has more than 12 years of medical practice and clinical research experience. Her focus has been in dermatology and she has been actively involved in the surgical and chemotherapeutic treatment of patients with melanoma. Prior to joining ICON, Dr. Goergen served as Medical and Drug Safety Advisor with Premier Research Ltd in Germany, providing support on medical and safety issues in clinical trials. Dr. Goergen' s medical device experience includes three years as Product Manager with Paul Hartmann AG in Germany, where she was responsible for all marketing activities for modern and traditional wound healing products for the Eastern European markets. She also worked as an Investigator for a post-marketing surveillance study. Dr. Goergen holds her MD from the Medical University of Bratislava. She speaks fluent Slovak, Czech, English, German, French and Russian. Her focused skills in dermatology and oncology will serve this project well as she provides medical knowledge and pharmacovigilance expertise for Genta and the European project team.
ROW Medical Monitor Australia and New Zealand
Luke E. Chung is the Medical Monitor in Singapore. Dr. Chung has over 6 years of experience working in the clinical medicine and 2 years of experience working in the clinical research industry. Prior to his involvement in the clinical research industry, Dr. Chung worked in clinical practice for over 5 years. Dr. Chung' s therapeutic experience includes Cardiovascular, Endocrinology, Nephrology, Neurology, and Smoking Cessation. His medical and business acumen, along with his fluency in English and Korean, will nicely support the GM307 protocol in Singapore.
Data Management Project Manager
ICON proposes Michelle O' Connell, M.S. , based out of our Newark, Delaware office to manage data activities for this protocol. Michelle brings over 9 years of management experience, including extensive oncology experience in
15
both solid and non-solid oncological indications. She holds technical expertise in SQL, SAS, and MedDRA, which she will use to maintain a thorough vigilance of all datasets. In addition to her experience in data management, Michelle has also worked at a medical university as a research program manager, where she advised developed, coordinated and supervised research activities of clinical studies conducted by Principal Investigators in the Radiology Department. Michelle' s educational credentials include a Master of Science Degree in Drug Regulatory Affairs and Health Policy. Her extensive knowledge in managing data for intricate therapeutic areas will provide established leadership for the data management portion of this global trial.
16
Study Timeline
Milestone
Target Date
ICON Involvement Begins
01 June 2007
First Patient In (FPI)
*
Last Patient In (LPI)
*
Treatment/Follow-up Ends: Last Patient Out (LPO)
*
Final Database Lock
*
Closeout Visits Completed
*
ICON Involvement Ends
31 March 2011
Total ICON Involvement
46 Months
The timeline shown above is based on the assumption that some sites may have FPI August 21, 2007, with the majority of sites should have FPI occur by October 2007.
17
Appendix I ICON Fees and Expenses
ICON incorporates an annual increase into its staff charge out rates to account for salary increases, cost of living increases, benefits, and competition for staff within the industry. Therefore, ICON has blended staff charge out rates across the lifetime of the project. The blending of rates has been ' weighted' and is in direct correlation to the timelines presented herein. Required modifications to the timelines will impact the rates accordingly.
Detailed Costs US
Clinical Research Management
Unit type
Number of Units
Unit Price (USD)
Total (USD)
Global Project Manager
Days
611
*
*
Lead CRA
Days
534
*
*
CRA
Days
2,301
*
*
CSA
Days
64
*
*
CR Assistant
Days
480
*
*
Unblinded Lead CRA
Days
118
*
*
Unblinded CRA
Days
482
*
*
Contract Administration
Per site
21
*
*
Payment Administration
Payment
861
*
*
ICOTrack Set-up
Study
1
*
*
ICOTrack Maintenance
Month
46
*
*
CLINICAL RESEARCH MANAGEMENT SUB-TOTAL
*
Medical Management
Unit type
Number of Units
Unit Price (USD)
Total (USD)
Medical Monitor
Days
30
*
*
Safety Monitor
Days
173
*
*
Medic ...
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