Evesse® “... Its why fruit is good for you!” Richard Wood Chief Executive Coressence Limited © Coressence 2007

Health Claim Criteria Characterised food component Food matrix and dietary context Epidemiology based evidence Data management / search / inclusion / exclusion criteria Substantiation based on human intervention studies Bio-active amount required and frequency of consumption Validated bio-markers and/or true end points Totality of available data © Coressence 2007

Characterised food component Evesse® Apples are flavanol-rich Evesse® contains the same flavanols as cocoa and grapes Evesse® blends with fruit juices, waters and low-fat yogurts Evesse® health claims relate to the “...maintenance of a healthy circulation...” © Coressence 2007

The Evesse® Apple Grown in the UK Non-Organic Organic 3 Products: Blending Juice Fructose Syrup Natural Red colour © Coressence 2007  True dietary context of apples in the UK Circa 80% of dietary fruit intake!

Food Matrix & Dietary Context Flavanol consumption from fruits – largest category Women consume more than men – 5 to 25% more! © Coressence 2007 mean =290 mg/d “consumers” Max >1000 mg/d “consumers” Women Men Range 300 to 1000 mg/p/d Source: Coressence analysis of UK NDNS data combined with US DA Flavanol database 2007

Food Matrix Model Source: Coressence analysis of NDNS data 2004 © Coressence 2007 Note: 1) 81% of potential consumers could consume 505 g/day of foods containing Evesse 2)Maximum mean daily consumption of active flavanols = 150 mg/day 3)50% of UK mean consumption or 13% of UK maximum consumption

Food Matrix Model © Coressence 2007 Note: Food intake model assumes Evesse is added at bio-active amount to each group

Antioxidant Measures  In-vitro tests for antioxidants don’t account for:  Bioavailability  i.e. The affect of absorption into the circulation. High degree of polymerisation = low bioavailability but High ORAC value!  Metabolites  i.e. The metabolites in circulation are not those tested by the assay!  High ORAC values can have Low bioavailability  Low ORAC values can have High bioavailability © Coressence 2007 Note: Applies ORAC,TAC, TRAP and FRAP assays

Health Claims Article 13.1 Claims Based on generally accepted science Article 13.5 Claims Based on newly developed science with IPR protection Article 14 Claims Disease Risk Reduction and/or child development & health Scientific substantiation Article 6 © Coressence 2007

Online Search – Maintained Records Online search of PubMed Online Search on “key words” Total number of Peer Reviewed Publications 38,285! © Coressence 2007 Note: Based on EndNote X1 software

Peer-reviewed Publications © Coressence 2007 Nobel Prize

Epidemiology – is useful Meta Analysis of included studies Included studies contain those used in wholegrain meta analysis i.e. Same cohorts, same validated food intake questionnaires and same follow-up period! Meta Analysis studies ranked by date demonstrates improved flavanol identification of food consumption Meta Analysis plotted as “forest plot” to show Risk Ratios © Coressence 2007

Meta-Analysis Stroke only 34,489 postmenopausal women Iowa Women’s Health Study 45,000 Kuna Indians in San Blas compared to mainland Panama Favours Control  0.72 Risk Ratio Point Size ~ significance Neutral  Favours Flavanols 0.52 Kuna Indian Risk Ratio Total Cohort subjects (excluding duplicate analysis) = 3,087, key studies included Meta Analysis includes studies based on CHD, MI & stroke endpoints. Includes studies used in wholegrain Meta Analysis. More recent studies have picked out Flavanol consumption data - USDA Flavonoid Database (2007) © Coressence 2007

Human intervention studies Criteria Included Studies 1990 – 2007 Bioavailability – i.e. Absorbed from food group – only double blind, randomised, crossed over studies 178 studies, 20 main studies selected “Flavanol monomers are absorbed as metabolites” Vasodilatation – i.e. Increased vascular compliance – only double blind, randomised, placebo controlled cross-over studies 145 studies, 56 main studies selected “Flavanol monomers enhance eNOS induced vascular relaxation helping to reduce arterial stiffness” © Coressence 2007

Vascular compliance © Coressence % increase in brachial artery diameter Impaired endothelial cell function triggers the development of plaques in blood vessels... Improved vascular compliance reduces the formation of plaque deposits and improves the circulation... People who eat flavanol-rich fruit have more compliant vasculature... “...Its why fruit is good for you!”

Pre-clinical Trials - Evesse Organic Juice Trials Low-fat Yogurt Trials Note: 1)Organic juice + 1mg/kg (body weight) Evesse 2)Low-fat Yogurt + 70 mg of Evesse 3)Based on photoplesmography © Coressence 2007 Equal to 4% vasodilatation Control Active

Pre-clinical Trials - Evesse Organic Juice Trials Low-fat Yogurt Trials Arterial Stiffness Index Vascular Age © Coressence 2007

Human & Animal Trials © Coressence 2007 Bio-active amount <1 mg/kg/BW HumanAnimal Source: SafeBridge Consultants Inc, Toxicological Risk Assessment 2007

Conclusions Evesse is a bioactive flavanol functional food with proven benefits An Article 13.1 health claim based on maintaining good circulation has been submitted to the FSA / EFSA Due diligence allows Coressence to support its health claim with good science Further clinical trials to take place in 2008, including 12 month intervention beginning January 2008 Other epidemiology and historical epidemiology to be published in 2008 © Coressence 2007