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April-2005

CardiaBeatTM

Total Lipid Management for a better health

in foods and supplements

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Current population trends

• Diabetes; Obesity; CVD are turning into an epidemic.

• They are associated with: age, modern diet and life-style.

• They are a major source of morbidity and mortality and health-care expenditure.

• They are growing!

• They have a common denominator.

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HighLDL

HighTG

Oxidative stress Low

HDL

Blood Pressure

Diabetes

Obesity

CVD

HighCholesterol

Abnormal Lipid Levels

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Specific Diabetic and weight-Loss needs.

• Main product categories: low-carb, “slow release”, low calorie, glucose management.

• Products are usually loaded with fats to ensure taste andsatiation

• Treated with low sugar diet and lipid-loweringmedications.

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CholesterolManagement

Current Solutions

Glucosemanagement

TG management

Side Effects

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The Opportunity• Unmet need

• Awareness • Compliance

• Protection

• Future

HighLDL

HighTG

Oxidative stress

LowHDL

Blood Pressure

HighCholesterol

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The solution: CardiaBeatTM

Comprehensive effect.

Fast effect.

Natural.

Based on clinical trials and animal models.

Proprietary by Enzymotec.

Total lipid management

DrinksBars

FunctionalOils

Dairy

Soy Milk

Shakes

Proactive Fat

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TitleObjectiveCodePriorityStatus

"Enzymatic modification of sterols"

ProcessUS 10/240546April, 2000pre exam (Public)

"Method of fractionation of phytosterol esters in oil and products obtained thereby"

ProcessUS 10/888087January, 2002

pre exam (Public)

“Oils enriched with diacylGlycerols and phytosterol esters for use in the reduction of cholesterol and triglycerides”

Health benefits for lowering cholesterol, triglycerides and oxidative stress, incl. diabetes.

WO04/069150February 2003

under exam (Public)

“Weight managementthrough lipid Compositions”

Weight management effect.

IL 163447August, 2004

pre exam (confidential)

“Food products for diabetics”

Food products for diabetics containing CVD health ingredients.

IL 163418August, 2004

pre exam (confidential)

Patents

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Regulatory• CardiaBeatDS

- NDI.

• CardiaBeatFF - self-GRAS.

• EU - Sufficient equivalence.

• Korea – New regulations are still in hold.

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Technical Background

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Cardiovascular Disease cascade

1. Plaque formation is caused by:• Large lipid pool; and

• Abundant macrophages.

2. This Phenomenon could be prevented by inhibition of its main causes.

LDL Ox-LDL Plaque

OxidationIncreased Risk for CVD Morbidity and Mortality

High Cholesterol

High TG

HDL

Macrophage

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• Lowering of LDL and TG levels.

• Increasing the levels of HDL to perform reduction of Ox-LDL back to LDL.

• Inhibition of oxidation and macrophage to foam cells generation processes.

• Conclusion: Only a comprehensive effect will effectively reduce CVD risk.

The Ideal Solution LDLOx-LDL Plaque

Oxidation

Increased Risk for CVD Morbidity and Mortalityj

High Cholesterol

High TG

HDL

Macrophage

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Immediate/Short term benefits Long term benefits

Lower risk for coronary artery disease

Lower risk for Type 2 diabetes

Lower risk for obesity

Decreased incidence of cancer

Lower risk for Pulmonary disorders

Reduce total LDL “bad’ Cholesterol

Effect on HDL “good” cholesterol and

more importantly HDL/LDL.

Reduce Triglyceride Levels

Weight control

CVD – The Ideal Solution

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Product Positioning

Dietary supplements Functional foods

Based on Sterol-DAG delivery system.

Better than existing solutions.

Cost structure adequate for foods.

Taste/odour and physical properties good for foods.

Have been tested on: bars, spreads, cooking oil, mayonnaise.

Based on sterol-DHA delivery system.

Potent and superior

Expensive

Taste/odour limit food applications

Have been tested on: bars, spreads, cooking oil, mayonnaise.

CardiaBeatDS CardiaBeatFF

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Clinical trials

TrialObjectiveVehicleOutputBy

Animal Model

To study the effect on ApoE-

mice, compared with olive/sterol-esters.

FoodReduction in Cholesterol, Oxidative stress and TG, compared to controls

Prof. Miki Aviram

HumansTo study the effect on healthy volunteers*, compared to olive/sterol-esters/DHA.

FoodReduction in Cholesterol, Oxidative stress and TG, compared to controls

Prof. Peter Jones

HumansTo study the effect on over-weight volunteers, compared to control.

FoodTBDDr. Nachum Vaisman

Animal Model

To study the effect on diabetic model, compared with control.

FoodTBDProf. Ehud Ziv.

HumansTo study the effect on diabetic patients, compared with control.

Dietary supplement

TBDProf. Raz

* - Hypercholesterolemia. Mildly overweight.

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Atherosclerosis in a Mouse Model

Professor Michael Aviram, Head, Lipid Research Laboratory, Rambam Medical Center and Technion Faculty of Medicine

ParametersBase stock oil

carDiabeat

Cholesterol-

Triglycerides- Oxidative stress in plasma

- Oxidative stress in macrophages

-

Qualitative comparison of effect

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-15

-10

-5

0

5

10

TG

TC

LDL TC/HDL

TBARS

Fish Oil

Plant sterol esters

Cardiabeat FF

HDL/LDL(ApoA/B)

Summary of Effect by CardiaBeatFF

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Qualitative Summary of effects

SolutionDaily intake

Heath score

LDLCholesterol

HDL

HDL

LDLTG

Oxidative stress

CLA0.7-8 gr-4---0/+-

Omega3Max. 2 gr00--+++/-

DAG15 gr+2000++NA

Phytosterol-esters

1.3 gr+4++++00

CardiaBeatFF

2-5 gr+8+++++++

+ Positive effect; 0 No effect; - Negative effect

As shown by our clinical trials and by others.

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• CardiaBeatFF reduces TG levels, while

maintaining similar effect on LDL lowering and maintenance of LDL/HDL ratio.

• CardiaBeatFF shows anti-oxidation properties.

Solution by CardiaBeatFF

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The Solution: CardiaBeatFFTotal lipid management

Daily consumption/RDA

2-5 gr

Sterol-esters1.3 gr*

DAGMax 800 mg

Proprietary.

Cost effective.

Platform allows future health claims and applications.

Esters and DAG are predominantly MUFA instead of Omega-6.

Process ensures trans-free esters.

The product can use health claims and healthy appeal of sterols and DAG.

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-50

-40

-30

-20

-10

0

10

20TG

TC

LDL

HDL/LDL(ApoA/B)

TC/HDL

TBARS

Fish Oil

Plant sterol esters

Cardiabeat DS

Summary of Effect by CardiaBeatDS

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Qualitative Summary of effects

• CardiaBeat is the only solution that simultaneously improves all CVD risk factors.

• Other solutions such as Fish oil or sterols offer partial solution and in some cases increase risk.

SolutionDaily intake

Heath score

TotalCholester

olLDL

Cholesterol

HDL

HDL

LDL

TG

Omega3Max. 2 gr+1+0--++

Phytosterol-esters

1.3 gr+6++++++0

Mix2.5-3 gr+5-6++++0/-0++

CardiaBeatDS

2 gr+11+++++++++++

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• Fish oil has a negative effect (increase) on Total/HDL ratio while sterols has a marginal effect only.

• CardiaBeat showed a strong positive and significant effect on LDL/HDL ratio, which cannot be delivered by any of its components or their mix. This is beyond maintaining efficacy on LDL and Total Cholesterol reduction.

• CardiaBeat showed 40% reduction of TG level over DHA/mix*.

Solution by CardiaBeatDS

* - This is likely to show significance in larger population or higher TG enrolment criteria (our trial enrolled healthy volunteers).

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Other benefits by CradiaBeatDS

Regarding main lipid factors, current science base supports the following features of CradiaBeat:

• A smaller capsule size - from 2.5-3 gr/day compared with 2 gr/day only.

• Alteration of CRP levels.

• Other expected benefits include: reduce vitamin loss and alteration of DHA bioavailability, leptin levels and other inflammation markers.

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The Solution: CardiaBeatFFTotal lipid management

Daily consumption/RDA

2 gr

Sterol-esters1.5 gr

DHA650 mg

DAGApprox. 150 mg

Proprietary.

Cost effective.

Platform allows future health claims and applications.

The product can use health claims and healthy appeal of sterols and DHA.

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Final comments

• High level of “Good” cholesterol is important for health; and

• Balancing LDL “bad” and HDL “good” cholesterol levels is crucial for reducing CVD risks.

• Other solutions has a negative or no effect on this balance.

• CardiaBeat has a stronger effect than others, for example: 40% better TG lowering than fish oil.

We see the following main points to address benefits:

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The Functional food opportunity

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ConfidentialADM's Enova cooking oil approved as a novel food in EU

Date Posted: 1/26/2005

25/01/2005 - - Emerging research looks set to position omega-3 fatty acids as a new ingredient for weight loss foods and supplements,

Feb 15,2005-Yoplait® introduces the first yogurt in U.S. with cholesterol lowering plant sterols.

08/02/2005 - - Obesity increases the risk of a mother giving birth to a child with neural tube defects, even if they are receiving folic acid, suggests a new study.

Forbes cholesterol-lowering ingredient approved in EU 11/16/2004 - The Canadian sterol maker Forbes Medi-Tech has gained authorisation to sell its Reducol ingredient for use in milk-based drinks in the European Union, with further food categories expected to follow shortly.

Supplement CLA may help reduce body fat Conjugated linoleic acid, or CLA, a fatty acid found primarily in meat and dairy products, may help reduce body fat mass, according to new research (American Journal of Clinical Nutrition, 2004, vol. 79, no. 6). Researchers from the Scandinavian Clinical Research center found that during a yearlong double-blind and placebo-controlled clinical trial, participants who consumed 4.5 grams of CLA per day significantly decreased their overall body fat mass.

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Case studyCase study

• Diabetic nutrition.

• Key Points: Weight Loss, Slow sugar

release, low calorie, balanced nutrition.

• 3-10% fat. Part of it is saturated fat.

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CardiaBeatTM for functional foods

Health bars

Dairy-based products and especially yogurts.

Soy-milk

Yellow fats and oils, including cooking oils

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The Dietary supplements opportunity

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CardiaBeatTM for dietary supplements

• Growing concern for Obesity, Diabetes and CVD.

• Growing Awareness for self and preventive Care.

• Emerging trends of DHA/Omega 3 and Sterol-esters.

• The market is looking for new and better solutions.

• CardiaBeat takes advantage of existing solutions, while leveraging their disadvantages.

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CardiaBeatTM by Enzymotec

• Proprietary science and technology.

• Regulatory procedures finalized.

• Continuous support of science and technology.

• Platform technology that enables future expansion.

• Applicability in various food products: bars, shakes, dairy…

• Science base to support future health claims.