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Shanghai Health Study Proposal for Bringing Study to Successful Closure Draft: August 16, 2006 Background: July 3l-Aug 2 2006, the investigators, Scientific Review Panel, and Ethics Review Panel met to evaluate progress towards meeting the study aims of the Shanghai Health Study. Members of the sponsoring companies attended as observers. Sponsors did not participate in the technical session. At about the same time, the sponsors received Dr. Irons and Dr. Wong's mid-year reports. Dr. Irons submitted a technical study update to the SRP and ERP. The sponsors received a financial report from Dr. Irons. While good progress is being made, there have been some challenges, which could cause the study to run longer than previously predicted. Loss of lab and exposure personnel is the most significant issue. Options: Irons Budget Additional $ Shell Share l8.3MM 0 0 l8.8MM +0.5MM o(take from contingency $) 19.3MM + ~ 1.0MM + ~ lOOK 22.3MM +~4.0MM + ~ 600-700K SHELL-MCCLURG-068150 Shanghai Health Study Proposal for Bringing Study to Successful Closure Draft: August 16, 2006 Background: July 31-Aug 2 2006, the investigators, Scientific Review Panel, and Ethics Review Panel met to evaluate progress towards meeting the study aims of the Shanghai Health Study. Members of the sponsoring companies attended as observers. Sponsors did not participate in the technical session. At about the same time, the sponsors received Dr. Irons and Dr. Wong's mid-year reports. Dr. Irons submitted a technical study update to the SRP and ERP. The sponsors received a financial report from Dr. Irons. While good progress is being made, there have been some challenges, which could cause the study to run longer than previously predicted. Loss of lab and exposure personnel is the most significant issue. Options: Irons Budget Additional $ Shell Share Impact on Time Line Impact on Case Accrual Achievements Positives Negatives Option 1 18.3MM 0 0 0 Stop case accrual YE06 NHL = 336 Option 2 18.8MM +0.5MM o(take from contingency $) 0 Stop case accrual YE06 0 Exposure assessment not as robust NHL = 433 Option 3 19.3MM + ~ 1.0MM + ~ lOOK 0 Stop case accrual May 07 0 Exposure assessment completed NHL = 500 Option 4 22.3MM +~4.0MM + ~ 600-700K 0 Stop case accrual May 07 0 Exposure assessment completed 0 Full data analysis NHL = 500 0 Built and gifted to Fudan University state of art diagnostic lab 0 Provided free diagnostics to 1000s of Shanghai residents 0 First study to use WHO tumor classifications 0 Demonstrated commitment to learning about benzene 0 Publications Case Control Honor time line paper >400 AMLINHL 500 AMLINHL cases cases for Case Control Study <400 AMLINHL cases Do not achieve Do not achieve SHELL-MCCLURG-068151 protocols protocols Did not achieve Did not achieve study goals study goals SHELL-MCCLURG-068152 Shanghai Health Study Proposal for Bringing Study to Successful Closure Draft: August 16, 2006 Background: July 31-Aug 2 2006, the investigators, Scientific Review Panel, and Ethics Review Panel met to evaluate progress towards meeting the study aims of the Shanghai Health Study. Members of the sponsoring companies attended as observers. Sponsors did not participate in the technical session. At about the same time, the sponsors received Dr. Irons and Dr. Wong's mid-year reports. Dr. Irons submitted a technical study update to the SRP and ERP. The sponsors received a financial report. SHELL-MCCLURG-068153 Shanghai Health Study Recommendation to API Executive Committee April 3, 2007 Shell supports request for additional funding up to $9.1M - Shell share is 1.6M API Exec Comm approved funding in Dec Sponsors recommending: - Advance of up to $2M to support lab while new contracts are being executed CinPathogen - Fudan University contract executed CinPathogen - University of Colorado letter of understanding received API - Sponsor contract amendments ready for signatures - CinPathogen as new entity for funding Delaware Certificate of Incorporation in hand State of Colorado Certificate of Good Standing in hand DRAFT SHELL-MCCLURG-068154 Shanghai Health Study - December 15,2006 Study Status o Case Control o Molecular Epi o Disease Progression Current Desired 425 AMLI 240 NHL cases 500 each Factory worker evalutions Biomarkers 40% AMLsINHLs followed Knowledge in Benzene Poisoning and MDS progressing to AML Funding Request - Up to 10.4MM- Shell's share about $2MM Funding Level recommended by sponsors' oversight committee - Up to 9.IMM- Shell's share about $1.7MM Options considered by Sponsors No additional $ Fully Fund Manage Risk Recommended Option Cost limited to current - 5MM (Shell share) Shell share increased to $2MM Support additional funding if conditions met Contractual exposure Future $ increases unknown Shell Share increased by $1.7MM Reputation SHELL-MCCLURG-068155 Shanghai Health Study - December 15,2006 Conditions to support additional funding agreed by consortium - Robust QAIQC process to be implemented; led by Dr Rice, Scientific Review Panel chair, with Dr. Wong, Case Control Study principal investigator and Judy Baldwin, professional QAIQC expert. QAIQC Team has full access to study database. - Case Control study accruals to achieve 500 AMLs and 500 NHLs or end by YE07whichever comes first - Progress on Disease Progression and Molecular Epi studies based on funding - Grant payments to University of Colorado tied to study progress - University of Colorado funding capped - Benzene Health Research Consortium (BHRC) to terminate YE08 - Monthly metrics on case accruals reported to Scientific Review Panel and BHRC Oversight Committee SHELL-MCCLURG-068156 Shanghai Health Study - December 15,2006 Study Time Line - 07: Complete data collection - 08: Data analysis Closing Ceremony in Shanghai (cultural and ethics expectation) Sponsors consortium terminates - 08-09: Publications SHELL-MCCLURG-068157