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DSM Nutritional Products
Dr. Bernd Mussler, Innovation Project Director
March 11, 2014
Fruitflow®
- the EFSA supported natural heart
health ingredient

2. Page 2
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

4. FOR INTERNAL USE ONLY
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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
Atherothrombosis
Atherosclerosis

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

7. FOR INTERNAL USE ONLY
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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

8. FOR INTERNAL USE ONLY
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Tomatoes an integral part of the
Mediterranean diet
• Tomatoes are important components of the Mediterranean diet
8

9. 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

10. What is Fruitflow®
Fruitflow I Fruitflow II SD
Liquid 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

11. 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 to
avoid 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

12. Whole blood
Platelet labeled with fluorescence marker
Glass tube coated with collagen
Collagen triggers platelet aggregation
100 µg of Fruitflow reduces platelet aggregation
Fruitflow ®
–How does it work?
Whole blood
Platelet labeled with fluorescence marker
Glass tube coated with collagen
Collagen triggers platelet aggregation
In the consumer world…
In the scientific world…

13. Studies that Provide Evidence for Fruitflow®’s
Ability to Reduce Platelet Aggregation
References Design
N / Gender /
Study Population
Duration /
Dosage
Outcomes measured Significant effect
1. O’Kennedy et al
2006a
R, SB, PC
Cross-over
23 / M F
Healthy
Single dose
18 g WSTC I
Platelet Aggregation
PT and TCT
+
-
2. O’Kennedy et al
2006b
R, DB, PC
Cross-over
93 / M F
Healthy
Single dose
18 g or 6 g WSTC I
Platelet Aggregation
PT and TCT
+
-
3. O’Kennedy et al
(unpublished)
Single
intervention
15 / M F
Healthy
Single dose
3 g WSTC I
Platelet Aggregation
PT and TCT
+
-
4. O’Kennedy et al
(unpublished)
R, DB, PC
Cross-over
22 / M F
Healthy
28 d
6 g WSTC I
Platelet Aggregation
PT and TCT
+
-
5. O’Kennedy et al
(unpublished)
R, DB, PC
Cross-over
45 / M F
Healthy
Single dose
6 g WSTC I
150 mg WSTC IIa
150 mg WSTC IIb
Platelet Aggregation
PT and TCT
+
-
6. O’Kennedy et al
(unpublished)
R, positive C
Cross-over
20 / MF
Healthy
Single dose or 5 d
3 g WSTC I in 250 mL
12 g WSTC I in 1 L
Platelet Aggregation
PT and TCT
+
-
7. O’Kennedy et al
(unpublished)
R, postiive C
Cross-over
9/ MF
Healthy
Single dose
3 g WSTC I in OJ
150 mg WSTC II in Yoghurt
600 mg WSTC II in Yoghurt
Platelet Aggregation
PT and TCT
+
-
8. O’Kennedy et al
(unpublished)
R, DB, PC
Cross-over
46/MF
Healthy
75 mg low-dose aspirin (8
d)
6 g WSTC I (1 d)
Platelet Aggregation
PT and TCT
+
-
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),

14. How is Fruitflow®
produced?
MillingTomato
Storage
Ultra-
filtration
concentrate
permeate
Fruitflow® I
Evapo
-ration
Pasteurization
Decanter
Fruitflow®
II SD
Fruitflow®
I
Resin
Spray
drying
Fruitflow®
II
Water,
Sugar

15. 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®
case
Fruitflow®
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
20
Selected innovation platforms
Ideas 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

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22. Thank you for your attention!

23. Page 23
The Fruitflow®
Team is not shy to take action….
We invite you to join!

24. Fruitflow acts on different
activation 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