dsm the fruitflow case

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DSM Nutritional Products

Dr. Bernd Mussler, Innovation Project Director

March 11, 2014

Fruitflow® - the EFSA supported natural heart health ingredient

Agenda

• The Market opportunity – Heart Health Market

• The Product opportunity– What is Fruitflow® – How does it work

• The Fruitflow case

• Learnings– Product qualifiers– DSM portfolio opportunities

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Heart health is a major consumer concern

• Heart health is one of the top conditions for which consumers buy supplements

• 50 million consumers in the US take anti-thrombotic drugs daily to “thin the blood”

• 58% of consumers are concerned about stroke

• 71% are concerned about Deep Vein Thrombosis

Fruitflow offers new opportunities:

• A NEW and DIFFERENTIATED heart health solution based on blood circulation

• A new segment within the heart health category with significant growth potential

• Current nutritional solutions for Heart Health focus on cholesterol and blood pressure > BLOOD CIRCULATION is the crucial missing linkPaint-topics.org 2010

FOR INTERNAL USE ONLY

Plaques inside the coronary arteries sometimes break open or "rupture." This is what causes most heart attacks. When a plaque breaks open, it causes a blood clot to form inside the artery. As the clot grows, it can completely block off the flow of blood through the artery. That means that the tissue on the other end of the clogged artery does not get the blood and oxygen it needs, so it gets damaged or dies.

Critical cardiovascular events

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Metabolic diseases are associated with chronic inflammation and platelet activation

Adapted from Davi et al. 2007• Chronic inflammation induces platelet activation

• Activated platelets release pro-inflammatory mediators that amplify the inflammatory response and platelet activation

AtherothrombosisAtherosclerosis

Huge population requiring anti-platelet therapy…but the risks may outweigh benefit


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The Mediterranean diet - a healthy diet

• Vegetables– leafy vegetable raw and cooked– raw tomatoes– onion– garlic and other vegetables….

• Fruits (fresh in summer, dried in winter)• Legumes (beans..)• Grain (whole wheat bread), nuts, Pasta• Small amounts of meat• Fermented dairy products (cheese,

yogurt)• Moderated alcohol drinking (red wine)• Olive oil• Fish

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Typical Mediterranean diet Mediterranean diet pyramid


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Tomatoes an integral part of the Mediterranean diet

• Tomatoes are important components of the Mediterranean diet

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What is Fruitflow®

• The first natural, scientifically sustantiated solution for healthy blood flow

• Fruitflow® is a breakthrough ingredient. In 8 human trials it has shown to reduce platelet aggregation and improve blood flow and works in 97% of subjects. The effect takes place within 1,5 hours of consumption

• It is a water-soluble, tomato based concentrate containing multiple active constituents

• Fruitflow® was the first ingredient with an proprietary EFSA Art 13.5 health claim:

“Helps maintain normal platelet aggregation, which contributes to healthy blood flow”

• Natural, healthy and safe

• Highly stable and water-soluble, low flavour, odour and colour profile and suitable for use in food, bevergages & dietary supplements

What is Fruitflow®

Fruitflow I Fruitflow II SDLiquid form (Syrup) Powder format

Active dose: 3 g / 250 ml drink

Active dose: 150 mg/daily dose or portion

Safe and stable (24 months at 8°C)

Safe and stable (> 18 months)

Simple sensory masking

Substantially sugar-free, simple sensory masking

Food & Beverages Dietary Supplements, Food & Beverages

Brown to dark brown liquid

Brown to dark brown free flowing powder

Commercial forms of Fruitflow® Fruitflow® composition

Non activated /smooth platelet Activated / spiky platelet Blood clot

•Platelets can become “spiky” i.e. more prone to clotting due to a variety of factors like stress, overweight, high cholesterol.

•Fruitflow works by keeping blood platelets smooth toavoid aggregation inside blood vessels.

•Fruitflow does not disrupt the rest of the blood clotting process so clotting will still take place as usual after injury.

•Three major factors in cardiovascular disease: cholesterol, blood pressure and platelet aggregation, the cause of blood clots.

•Fruitflow® is the only functional food ingredient addressing platelet aggregation

Fruitflow acts on the first stage of the clotting process: Platelet activation

Whole bloodPlatelet labeled with fluorescence markerGlass tube coated with collagen Collagen triggers platelet aggregation100 µg of Fruitflow reduces platelet aggregation

Fruitflow ® –How does it work?

Whole bloodPlatelet labeled with fluorescence markerGlass tube coated with collagen Collagen triggers platelet aggregation

In the consumer world…

In the scientific world…

Studies that Provide Evidence for Fruitflow®’sAbility to Reduce Platelet Aggregation

References Design N / Gender /Study Population

Duration /Dosage Outcomes measured Significant effect

1. O’Kennedy et al 2006a

R, SB, PCCross-over

23 / M FHealthy

Single dose18 g WSTC I

Platelet AggregationPT and TCT

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2. O’Kennedy et al 2006b

R, DB, PCCross-over

93 / M FHealthy

Single dose18 g or 6 g WSTC I


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3. O’Kennedy et al (unpublished)

Single intervention

15 / M FHealthy



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R, DB, PCCross-over

22 / M FHealthy

28 d6 g WSTC I


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R, DB, PCCross-over

45 / M FHealthy


150 mg WSTC IIa150 mg WSTC IIb


+ -


R, positive CCross-over

20 / MFHealthy

Single dose or 5 d3 g WSTC I in 250 mL

12 g WSTC I in 1 L


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R, postiive CCross-over

9/ MFHealthy

Single dose3 g WSTC I in OJ

150 mg WSTC II in Yoghurt600 mg WSTC II in Yoghurt


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R, DB, PCCross-over

46/MFHealthy

75 mg low-dose aspirin (8 d)

6 g WSTC I (1 d)


+-

Abbreviations: R=randomized, DB=Double-blind, SB=Single-blind, PC=Placebo-control, C=Control, M=Male, F=Female, PT=Prothromin, TCT=thrombin clotting time, WSTC=water-soluble tomato extract (Fruitflow),

How is Fruitflow® produced?

MillingTomato

StorageUltra-filtration

concentrate permeate

Fruitflow® IEvapo-ration

PasteurizationDecanter

Fruitflow® II SD

Fruitflow® I

ResinSpray drying

Fruitflow® II

Water,Sugar

Analytics of Fruitflow

• Fruitflow is a natural multi-component product

• Representative marker selected

• Adenosin• Chlorogenic acid• Rutin

• 3 major compound clusters

• Nucleosides (AF 1)• Polyphenols (AF 2)• Flavonoids (AF 3)

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The Fruitflow® caseFruitflow® was developed by Provexis and licensed to DSM

•Original research started in the Rowett-Institute in Aberdeen in the lab of Prof. Asim Dutta-Roy•Provexis started the scientific and technical development of Fruitflow® in 1999•Provexis is a listed Company at the London stock exchange (AIM)

• In 2008 DSM Venturing became major shareholder of Provexis (and still is) • In 2009/10 Fruitflow® was the first Product that achieved a § 13.5 proprietary EU Health

Claim after a rigorous evaluation process• Since 2010 Fruitflow ® is commercialized by DSM globally• In 2013 Fruitflow II (powder) was globally launched

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DSM Product Qualifiers Sourcing:

•Natural sourcing to reduce regulatory hurdles globally•Attractive food source with established intake in Europe prevents Novel Food•Non-selective extraction preferred only based on food processing (physical) approved means

•No chemical modification, no GMO•Food quality side stream sourcing preferred

Safety:

•History of safe use (food source)•Process safety (food technology)•Pre-clinical safety•Human safety demonstrated in the clinical studies•Profiling of potential contaminants (Pesticides, environmental insults like PAH, mycotoxins)

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DSM Product Qualifiers Differentiation by efficacy:

•Effective dose: < 500 mg of active•Mode of action understood•Proof of principle in vivo, better in human demonstrated•Set of human studies in healthy people conducted according to scientifically accepted standards with a reasonable amount of subjects•Accepted clinical endpoint applied

Entry barriers:

•Sourcing and/or backward integration•Trade secrets•Use and process patents•EU Health Claim § 13.5

Application aspects:•Color•Smell •Taste•Stability•Solubility

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Key success criteria

Product side stream available?Evidence of Health Benefit?

DSM to support with:•Scientific and technical know how•Regulatory know how &•Global market reach

Attractive or exotic food source available?

Link to epidemiological data possible?

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Confidential

CONFIDENTIAL

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Selected innovation platformsIdeas are very welcome

• New nutritional lipids

• Vitamers (Vitamin like products, co-factors, etc.)

• Ingredients to prevent (food) allergy/intolerances

• Natural coloration (blue/red/purple)

• Ingredients that stimulate immune function

• Fibers

Thank you for your attention!

The Fruitflow® Team is not shy to take action….

We invite you to join!

Fruitflow acts on differentactivation pathways

adapted from Rivera et al. 2009

Main platelet receptor-ligand interactions

Aspirin

• Fruitflow works on multiple aspects of the initial clotting mechanism

• Aspirin works on only one specific pathway

• Fruitflow effect is reversible, Aspirin effect is not

• Fruitflow exerts ~30-50% the inhibition induced by LD-aspirin

Conclusions

Fruitflow lowers expression of active form of GIIb/IIIa

ARA

COX

Irreversible inhibition of COX

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