REGULATION OF APPETITESatiety peptides

Clinically

Proven

FOOD CONSUMPTIONOBESOGENIC ENVIRONMENT UK is one of the fattest country in Western Europe

1/3 of UK adults underestimate their own calorie intake (Office of national statistic data)

Why?

"Some people forget what they've consumed” Public Health England chief nutritionist Dr Alison Tedstone said

▪ Eating habits▪ Restaurant eating▪ Portion sizes vary▪ Snacks on the go▪ Drinks

Latest obesity rates

HEALTHY ENERGY BALANCE

Satiety

Body

weight

▪ Obesogenic environment

▪ Overweight and obesity are linked to a disequilibrium

between food intake & energy expenditure

▪ Weight gain can be a consequence of overeating by just

100 calories a day

Satiety noun:

End state that occurs at the meal’s end to inhibit further eating

behavior.

MECHANISM OF APPETITE REGULATIONPHYSIOLOGICAL APPETITE RETRO-CONTROL

Decrease in

glucose level Blood

Production of

ghrelin

Stomach

Reduction in

leptin level

Adipose tissue

Hypothalamus

Vagus

nerve

Reduction in

ghrelin level Stomach

Distention of

the stomach

Production

of insulinPancreas

Increase in

PYY, CCK, GLP-1Gastrointestinal

tract

- +

Inter-meal

-

Sensorial

stimulation

SATIETY

NPY secretionHypothalamus

Decrease in

NPY secretionHypothalamus

Food intake

APPETITE+

Central control

Peripheral control

MECHANISM OF APPETITE REGULATIONPHYSIOLOGICAL APPETITE RETRO-CONTROL

Decrease in

glucose level Blood

Production of

ghrelin

Stomach

Reduction in

leptin level

Adipose tissue

Hypothalamus

Vagus

nerve

Reduction in

ghrelin level Stomach

Distention of

the stomach

Production

of insulinPancreas

Increase in

PYY, CCK, GLP-1Gastrointestinal

tract

- +

Inter-meal

-

Sensorial

stimulation

SATIETY

NPY secretionHypothalamus

Decrease in

NPY secretionHypothalamus

Food intake

APPETITE+

Central control

Peripheral control

ACUTE EFFECT

-

LONG-TERM EFFECT

-

-

DNF-10 SATIETY PEPTIDES FOR WEIGHT MANAGEMENTCOMPOSITION

Saccharomyces cerevisiaeYeast for bread or beer fermentation

Food-based< 10 kDa

S. cerevisiae NBRC (ex. IFO) 2346

Stability & activity validated

after heat treatment at 160°C/320°F

PR

OTE

OLY

SIS

YEA

ST

ULT

RA

FIL

TRA

TIO

N

CO

NC

EN

TRA

TIO

N

SP

RA

Y D

RY

ING

Non GMO Patented

500 mg

per day

SCIENTIFIC INVESTIGATION

11 publications

OVERVIEW

2009

MECHANISTIC TRIALS

30 women

20-28 years old

BMI ≥ 25

6 weeks

2 g/day in

sachet

20 women

20-28 years old

Body Fat ≥ 28%

4 weeks

1 g/day in

capsule

54 women/men

20-50 years old

BMI ≥ 25

10 weeks

1 g/day in

sachet

30 women

20-60 years old

BMI > 25

8 weeks

0.5 g/day in

capsule

2011 2014 2017

EXPLORATORY PHASE DEMONSTRATION PHASE

3 4

▪ 2008 - Appetite Suppressive Effects of Yeast Hydrolysate on Nitric Oxide

▪ Synthase(NOS) Expression and Vasoactive Intestinal Peptide(VIP) Immunoreactivity in Hypothalamus

▪ Effects of Yeast Hydrolysate on Hepatic Lipid Metabolism in High-Fat-diet-induced Obese Mice

▪ 2008 - Effects of Yeast Hydrolysate on Neuropeptide Y(NPY) and Tryptophan Hydroxylase(TPH) Immunoreactivity in Rats

▪ Safety study of yeast hydrolysate with below 10kDa Molecular weight in animal models

▪ 2004 - Yeast hydrolysate reduces body fat of dietary obese rats

▪ 2013 - Thermal stability of yeast hydrolysate as a novel anti-obesity material

▪ Yeast hydrolysate as a functional anti-obesity ingredient: appetite suppressive effects of yeast hydrolysate in food-deprived mice

PRE CLINICAL STUDIES

Serum Ghrelin Level (pg/mL)

MECHANISM OF APPETITE REGULATIONANIMAL MODEL

▪ Food intake is triggered by high level of ghrelin and

low level of leptin: DNF-10 significantly lowered

ghrelin secretion between meals.

▪ In the hypothalamus, DNF-10 intake lowered the

expression of NPY.

▪ The reduction of food intake was significant from thefirst day

Serum Leptin Level(pg/mL)

Neuropeptide Y (Optical density)

Cumulated food intake(g/100g of body weight)

0

500

1000

1500

2000

2500

3000

3500

4000

Control DNF-10 (0.5) DNF-10 (1.0)

0

50

100

150

200

250

300

350

400

450

500

Control DNF-10 (0.5) DNF-10 (1.0)

0

1

2

3

4

5

6

1 2 3 4 hours

**

*

*

**

0

20

40

60

80

100

120

CTR DNF-10 ( 0.1) DNF-10 (1.0)

**

GASTROINTESTINAL TRACTHYPOTHALAMUS

Control

2008 - Effects of Yeast Hydrolysate on Neuropeptide Y(NPY) and Tryptophan Hydroxylase(TPH) Immunoreactivity in Rats, Phytotherapy Research2015 – Yeast hydrolysate as a functional anti-obesity ingredient: appetite suppressive effects of yeast hydrolysate in food-deprived mice, Progress in Nutrition

CLINICAL STUDIESRANDOMIZED, PLACEBO-CONTROLLED CLINICAL STUDIES

0.5 g/day

Capsule

8 weeks

30 women

20-60 years old

BMI > 25

No specific exercise pattern and diet

recommendations

Food record (Can-Pro)

Published in Preventive Nutrition and

Food Science

Material:▪ Impedance bioelectrical balance

▪ Skinfold caliper

▪ Abdominal fat: computed tomography

▪ Impedance bioelectrical balance

4

1 g/day

Sachet

10 weeks

54 women/men

20-50 years old

BMI ≥ 25

No specific exercise pattern and diet

recommendations

Food record (Can-Pro)

Published in Nutrition

Materials:

3

Clinical study #3 - 2014 Clinical study #4 - 2017

SAFETY PARAMETERS

W1 W6

ΔW1-W6significance

W1 W6

ΔW1-W6significance

Blood markers

Glucose 70-140 mg/dL 92.6±6.3 96.7±10.1 N.S. 88.1±10.1 88.8±8.3 N.S.

Triglycerides < 150 mg/dL 105.3±43.3 116.6±54.4 N.S. 93.1±45.0 89.3±39.8 N.S.

Total CHOL < 200 mg/dL 206.3±18.6 200.7±25.0 N.S. 176.6±26.8 177.8±31.3 N.S.

HDL-CHOL ≥ 50 mg/dL 60.7±9.5 63.1±7.7 N.S. 58.0±12.3 59.6±15.7 N.S.

LDL-CHOL < 100 mg/dL 124.6±21.0 114.2±19.3 N.S. 100.0±23.8 99.8±28.4 N.S.

Placebo DNF-10

Healthy range* W1 W4

ΔW1-W4significance

W1 W4

ΔW1-W4significance

Blood pressure

Systolic < 120 mm Hg 118.9±4.6 117.7±2.9 N.S. 122.6±4.1 115.5±4.7 N.S.

Diastolic < 80 mm Hg 73.7±1.5 72.9±1.3 N.S. 73.5±1.8 73.1±2.5 N.S.

Heart rate 60-100 bpm 76.7±3.1 80.5±3.8 N.S. 77.2±1.7 79.7±3.0 N.S.

-600 kcal/day

-800

-600

-400

-200

0

200

400

600

W0 W1 W2 W3 W4 W5 W6 W7 W8

Daily energy intake variation(Kcal) W1-W8

CALORIC INTAKE REDUCTION

The reduction of calories per day is significant

from the first week of supplementation

Carbs intake variation (g)

Protein intake variation (g)

Lipids intake variation (g)*

** *

**

*

*

-80

-60

-40

-20

0

20

40

W0 W1 W2 W3 W4 W5 W6 W7 W8

-40

-20

0

20

40

W0 W1 W2 W3 W4 W5 W6 W7 W8

-40

-20

0

20

40

W0 W1 W2 W3 W4 W5 W6 W7 W8

The reduction of calorie intake

came mainly from carbs

Sweet appetence reduction

was measured

**

* *

*

* **

* * **

* **

* * **

* **

*Efficient from the first week

-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

-2

-1.5

-1

-0.5

0

0.5

-3

-2.5

-2

-1.5

-1

-0.5

0

0.5

1

Body weight variation (kg)

BODY WEIGHT AND COMPOSITION

Body fat mass(kg) △W1-W8

Fat mass ratio(%) W1-W8

*

*

-2.6kg

▪️

▪️

▪️

*

W1 W4 W8

35

36

37

38

39

1 2

100 % of the weight loss is fat mass

-5.9%

*

*Placebo

DNF-10: 0.5g

DNF-10: 1g

Weight loss is significant after the first month of supplementation

-1.5kg

W10

ANTHROPOMETRIC PARAMETERSABDOMINAL FAT MASS

Abdominal fat reduction by computed tomography

W1-W10

Total abdominal fat area (cm2) △W1-W10

Skinfolds reduction(mm) W1-W10

Waist circumference reduction(cm) W1-W10

-20

-15

-10

-5

0

*-17.3 cm2

Total abdominal fat reduced significantly with DNF-10 by 5%

▪ A reduction of 5 cm in abdominal circumference was achieved after 10 weeks ofsupplementation

-6

-4

-2

0

2

-6

-4

-2

0

2

**-4.9 mm -5 cm

KEY BODY WEIGHT LOSS BENEFITS

80% of the subjects thought less abouteating during the day than at the beginningof the supplementation

2014 Nutrition – Questionnaire: changes in appetite

Significant weight loss after the first month of supplementation

The weight lost is fat mass

Abdominal fat is significantly decreased

Waist circumference reduces by 5 cm

SUBJECT INSIGHTS

Significant reduction of caloric intake after the first week

CLINICAL STUDIESPUBLICATIONS & ARTICLES

▪ Appetite Suppressive Effects of Yeast Hydrolysate on Nitric Oxide Synthase(NOS) Expression and Vasoactive Intestinal Peptide(VIP) Immunoreactivity in Hypothalamus

▪ Effects of Yeast Hydrolysate on Hepatic Lipid Metabolism in High-Fat-diet-induced Obese Mice▪ Effects of Yeast Hydrolysate on Neuropeptide Y(NPY) and Tryptophan Hydroxylase(TPH) Immunoreactivity in Rats▪ Pet foods with yeast hydrolysate can reduce body weight and increase girth in beagle dogs▪ Safety study of yeast hydrolysate with below 10kDa Molecular weight in animal models▪ Yeast hydrolysate reduces body fat of dietary obese rats▪ Thermal stability of yeast hydrolysate as a novel anti-obesity material▪ Weight reduction effects of yeast hydrolysate below 10kDa on obese young women▪ Yeast hydrolysate can reduce body weight and abdominal fat accumulation in obese adults▪ Weight loss effect of yeast hydrolysate on obese young women▪ Low dose yeast hydrolysate in treatment of obesity and weight loss▪ Yeast hydrolysate as a functional anti-obesity ingredient: appetite suppressive effects of yeast hydrolysate in food-

deprived mice▪ The weight reduction effect of yeast hydrolysate SR101 on female college students▪ Weight reduction effects of yeast hydrolysate below 10 kDa on obese young women

2014 Nutrition 2017 Preventive Nutrition and Food Science

Publications

APPLICATIONS

Description Yeast hydrolysate: peptides from Saccharomyces cerevisiaeGMO Free, suitable for vegans

Active compoundsPeptides <10 kDa

Recommended dosage500 mg/day, 30 minutes before the meal

Labelling guidelinesUSA:

▪ Fermented Yeast Hydrolysate Peptides (Saccharomyces cerevisiae)

▪ Peptides complex (S. cerevisiae)

FR:▪ Peptide de levure de bière (Hydrolysat de Saccharomyces Cerevisiae)

Food-based Non GMO Patented

Applications

Compatible with probiotics:

water activity <0.3

FINISH PRODUCTS ON THE MARKETJAPAN

FINISH PRODUCTS ON THE MARKETKOREA

WEIGHT MANAGEMENT

These statements have not been evaluated by the food and drugs administration. This product is not

intended to diagnostic, treat, cure or prevent any disease.

Satiety peptides

WEIGHT MANAGEMENT

(Potential) conflict of interest

See below

Potentially relevant company relationships in connection with event 1

• Sponsorship or research funding2

• Fee or other (financial) payment3

• Shareholder4

• Other relationship, i.e. …5

FYTEXIA represents NeoCremar, the company funding the scientific investigation on DNF-10 described in this presentation.