MIRROR, MIRROR WHO IS THE FAIREST OF US ALL

B-WHITE™

MIRROR, MIRROR WHO IS THE FAIREST OF US ALL

SKIN RADIANCE/ SKIN LIGHTENING-

WHITENING/ ANTI-DARK SPOT

Why launching β-White™?

– Innovation

• Huge (and growing) market potential

• First to market!

• Mechanism of action: a breakthrough!

– Performance

• Lucas Meyer Cosmetics knowledge in whitening market

• Full Clinical Efficacy

• Biomimetic peptide

– Safety

• Targeted mechanism of action

• Excellent safety profile

• Batch to batch quality

• Introduction on Brightening Lightening Whitening market

• In Vitro assays – TGF-b receptor binding

– Inhibition of the constitutive production of melanin pathway : TRP1 – TRP2 – tyrosinase

– Inhibition of the tyrosinase activity

– Inhibition of melanin synthesis

– Morphological studies on melanocytes

• Clinical efficacy – Whitening and lightening efficacy

• Tolerance studies

• Applications

• Conclusion

Agenda - Whitening peptide

Why are we using skin whitening?

• Lighten age-spot and hyper-pigmentation

In North America and Europe skin whitening is seen more as a part of anti-aging treatment, to hide unwanted signs of aging like age spot, unhealthy life-style and pollution from the skin

• Whiter / lighter skin tone

– In Asia, lighter and even complexion is associated with higher social status (wealth & education) and a darker complexion has been associated with people who work in the field and are more exposed to the sun.

Vichy®

Market Opportunity?

Global skin lightening market = $13B Driven by new markets in the West and sustained growth in Asia Skin whitening market in Asia!!! 44% of Asian women have problems with brown spots, freckles and pregnancy marks

80% of Asian women report concern over skin darkening

Japan is largest market for skin whitening with 15-17% of all skin care

India & China are the fastest growing segments

Skin whitening market in USA!!! Skin brighteners represent $1.5B in 2008 are also contributing to the growth in anti-aging facial skincare

Why A Growing Trend?

Consumer Info • Who buys B/W/L and why?

- East: Consumers who desire a paler clearer complexion. Non-white Asian and African who want their skin tone to appear as light as possible

- West: Older women whom uneven pigmentation and skin texture caused by years of sun damage and fluctuating hormones are turning for brightening and radiance products.

- Concerns about aging: 1st Dry skin; 2nd Wrinkle; 3rd Age spot Many Different Applications

• Eveness of skin tone

• Anti-aging, Age spots

• Brightening/Whitening/Lightening (BWL)

• Body Care, …

Evolution of whitening products launches

Why A Growing Trend? Market Info

• Important evolution of the BWL products since 2004. High growth!

• Since January 2008: 2150 products were launched with the «BWL claim»

• 2 types of BWL products:

- Cheap, low-end and toxic products (high level of hydroquinone, bleaching agents) → sold legal and illegal market

- High-end skin BWL products develop to modify skin color and achieve youthful-looking skin

• No major innovation regarding the BWL active ingredients for the last couple of years

Skin lightening Market

Multi-usage cosmetic in Prestige & Mass market Skin care (face & body care), men care

Bella Aura Anti-Dark Spot Hand Care Cream

Spain

Superdrug Optimum Night Cream

UK

Oriflame Even Out Face Cream SPF20

UK

Ella Baché Radiance Solution

Australia

Innoxa Even Tone Body Cream

South Africa

Beau Ideal Skin Skin whitening

Taiwan

Market & Regulations

BWL products are driven by consumers desire for flawless complexion and safety concerns

Formulation / Ingredients

• Typical formulations contain mainy BWL active ingredients with complementary mechanism of action (vitamin C derivatives, arbutin, AHA, kojic acid, etc) with SPF

Successfull Whitening products

• Must deliver skin benefits: Paler, Even, Brighter Complexion & Reduce color of hyper-pigmented spot

• MUST HAVE AN EXCELLANT SAFETY PROFILE

Regulatory around the world

• What can be claimed?

- DEPENDS on country specificity & regulation! (ex: Quasi-drug status in Japan)

- «designed to reduce the appearance of dark spots and skin discolouration»

- «restore skin’s luminosity and glow»

- «contains … to slow down excessive melanin production»

Opportunity to develop innovative & safer BWL actives!

Focus on

b-White™

Skin Pigmentation

Pigmentation is determined by the amount & type of melanin in the skin

It can be influenced by:

1- Genetic constitutive pigmentation (African, Asian, Caucasian)

2- Facultative pigmentation : UV exposure via α-MSH activation

Skin Pigmentation Actors

Secondary Actors:

• Tyrosinase: Main enzyme involved in pigmentation cascade.

It regulates other enzymes like TRP-1 & TRP-2

• TRP-1 & TRP-2: enzymes involved in pigmentation

Ex: They represents the musicians

Result:

• Melanin pigments: Give the skin its color

Ex: Represent the MUSIC

MITF

Tyrosinase

TRP-1

TRP-2

Main Actor: MITF (microphtalmia-associated transcriptional factor)

• Role in constitutive pigmentation: responsible of phototype

• Role in facultative pigmentation: regulates skin response to UV

Ex: Represents the maestro in the orchestr

It directs the musicians to produce the music

De

rmis

Skin Pigmentation Pathways

SC

E

pid

erm

is

DE

J

keratinocyte

melanosome

melanocyte

- Facultative pigmentation inhibitor (α-MSH)

- Melanostatine®5

- Tyrosinase inhibitors

- Tyrostat™, Arbutin, Kojic acid, Hydroquinone

- ROS Scavengers

- Ascorbic acid (Tyrostat™ 11), tocopherol

- Signaling pathway between cAMP and tyrosinase

- Tretinoin, Vitamin A

- Inhibitors of melanosomal transfer

- Vit B3, soybean/milk extracts

- Accelerators of skin turnover

- Exo-T™, lactic acid, glycolic acid, AHA

How to Control Pigmentation

β-White™ Our Whitening Solution

Innovative encapsulated peptide!

Whitening peptide TGF-β Agonist

Whitening & brightening

efficacy through a new

pathway via the

inhibition of MITF

Phospholipid capsule (lecithin)

Helps the transport

of the peptide across the skin barrier

β-White™

Encapsulated peptide SAFE & POTENT

β -White™ Targeted Action

Tyrosinase TRP-1

TRP-2

β-White™ Main Action on MITF!!!!

What does it mean?

Can modulate the complete pathways of pigmentation

Can modulate the whole orchestra instead of limiting only few musician

MITF

Tyrosinase TRP-1

TRP-2

Majority of whitening agent act only on Tyrosinase

What does it mean?

Can modulate only one component of the pigmentation process

One musician stops but not the rest of the orchestra = there is still MUSIC

MITF

Skin Whitening Pathways

β-White™

In Vitro Functionality

TGF-b receptor

Binding of β-White™

β-White™ binds specifically to the TGF-β receptor

No free radiolabeled 125I-TGF-b 100% Binding of the radiolabeled 125I-TGF-b

0% binding of β-White™

100% free radiolabeled 125I-TGF-b 0% Binding of the radiolabeled 125I-TGF-b

100% binding of β-White™

125I-TGF-

b β-White™

β-White™ concentration (µg/m) 0 50 100 150 200

80

60

40

20

100

Inh

ibit

ion

of

the

na

tura

l T

GF

-b b

ind

ing

(%

)

120

TFG-β binding capacity

Modulation of the Constitutive Pigmentation Pathway

Test Protocol:

• Melanocytes were incubated with β-White™ at 0.01% for 30 minutes

• Intracellular proteins were extracted

• Proteins are transferred to a membrane and detected using antibodies specific to MITF

and tyrosinase with western blot methodology – MITF (microphthalmia-associated transcription factor): regulation melanin

production – Tyrosinase: key enzyme involved in melanin production

Modulation of the Constitutive Pigmentation Pathway

β-White™ decreases proteins expression implicated in the constitutive pigmentation

β-White™ decreases MITF and tyrosinase expression

Modulation of the Facultative Pigmentation Pathway

Test Protocol:

• Melanocytes were incubated with a-MSH and β-White™ at different concentrations

(0,01 – 0,1 – 1%) for 2 hours

• Intracellular RNA is extracted and quantified by RT-PCR methodology

• Specific antibodies were used to detected TRP-1, TRP-2 and MITF genes expression – TRP-1 & TRP-2 (Tyrosinase related protein): enzymes implicated in melanin

production

Modulation of the Facultative Pigmentation Pathway

β-White™ decreases proteins implicated in the facultative pigmentation

β-White™ decreases MITF, TRP-1 and TRP-2

expression in a dose dependant manner

Inhibition of Tyrosinase Activity

Test Protocol:

• Melanocytes were incubated with a-MSH and β-White™ at different concentrations

(0,01 – 0,1%) for 4 days

• Intracellular proteins were extracted and labelled with L-DOPA • The tyrosinase activity is evaluated by measuring the L-DOPA absorbance at 405 nm

(tyrosinase activity = amount of L-DOPA)

Inhibition of Tyrosinase Activity

β-White™ decreases the tyrosinase activity, thus reducing skin pigmentation

β-White™ decreases tyrosinase activity in a dose

dependant manner

Inhibition of Melanin Synthesis

Test Protocol:

• Melanocytes were incubated with a-MSH and β-White™ at different

concentrations (0,01 – 0,1 – 1%) for 4 days

• Intracellular proteins were extracted • The melanin pigment is detected by measuring the absorbance at 400 nm

(melanin synthesis = amount of brown pigment)

β-White™ decreases tyrosinase and melanin production for optimal whitening efficacy

β-White™ decreases melanin synthesis in a dose dependant manner

Inhibition of Melanin Synthesis

Test Protocol:

• Melanocytes were incubated with a-MSH and β-White™ at different

concentrations (0,01 – 0,1 %) for 4 days

• The morphology of cells were examined by microscopy • The dentricity and the number of melanosomes can be observed

Changes in melanocytes: Dendricity & Melanosome content

Changes of melanocytes: Dendricity & Melanosome content

a-MSH + 0.01% β-White™

Baseline

a-MSH

a-MSH + 0.1% β-White™

Melanosome

β-White™ prevents melanosome formation and thus, reducing the amount of melanin pigments for a lighter complexion

NO Melanosome

40X

Melanin Synthesis Comparative Study

Test Protocol

B16F10 melanocytes were incubated with 10μg/ml (1%) β-White™, 10μg/ml Vitamin C, 10μg/ml Arbutin for 96 hours.

Intracellular proteins were extracted

The melanin pigment is detected by measuring the absorbance at 400 nm

β-White™ decreases melanin synthesis with higher activity than Arbutin and Vitamin C

β-White™ has a higher efficacy than Arbutin &

Vitamin C

In Vitro Activities Summary

Binding to TGF β

Receptor

Decrease of MITF expression

Decrease of tyrosinase

activity

Decrease of TRP-1 & TRP-2

expression

Inhibition of melanin synthesis Reduction of dendricity &

melanosome content

Concentrations used: 0,01- 0,1%

β-White™

Clinical Efficacy

Whitening and Lightening

Clinical Efficacy on Skin Whitening / Lightening / Brightening

Protocol:

• 23 Asian subjects presenting at least one hyper-pigmented spot (age 33 to 55) • Application of a Cream with 5% β-White™, twice a day, for 56 days • Colorimetric measurements: analysis of the colorimetric parameter (L*) on the face at D0,

D28 & D56 by spectrophotometer • Clinical evaluation by dermatologist investigators with a skin color scale at D0, D28 & D56 • Questionnaire: closed questions on product efficacy at D0 & D56

Results on Skin Lightness (L*)

β-White™ induces significant skin lightening effect after only 4 weeks

Skin Lightness (L*): is defined as the perceived brightness of an object compared to a perfect white object. The L* value (luminance) gives the relative lightness ranging from total black (L=0) to total white (L=100)

100% of the subjects have a skin lightness increase!

Results on Skin Color

β-White™ induces significant skin lightening effect on pigmented spot after only 4 weeks

D0

D28

D56

Building effect!

-21%

-30%

Results on Skin Color

Additional information on skin color evaluation: - 10 people out of 23 have skin score higher than 5 - 5 people with 5 skin color score:

3 out of 5 have a reduction of 2.5 after 28 days

3 out of 5 have a reduction of 3.5 after 56 days

Average reduction of 2.1 after 28 days

Average reduction of 3 after 56 days

β-White™ induces significant skin lightening effect!!!!

D0

D28

D56

Results on Skin Color

Additional information on skin color evaluation: - 10 people out of 23 have skin score higher than 5 - 5 people with a 5 skin color score:

3 out of 5 have a reduction of 2.5 after 28 days

3 out of 5 have a reduction of 3.5 after 56 days

Average reduction of 2.1 after 28 days

Average reduction of 3 after 56 days

β-White™ induces significant skin lightening effect !!!!

D0 D28

D0 D56

Highest reduction

Results on Skin Color

β-White™ reduces the appearance of pigmented spots

Subject #7 (effect on hyperpigmented spot after 28 days)

Results on Skin Color

β-White™ reduces the appearance of pigmented spots

Subject #16 (effect on hyperpigmented spot after 56 days)

D0

Results on Skin Color

β-White™ lightens the overall skin tone after 56 days

Subject #18 (effect on the overall skin tone)

Results on Consumers Appreciation

Consumers agree that β-White™ makes the skin tone more uniform and brighter

Protocol

19 Caucasian women aged between 51 and 69 years old (mean=58) with pigmentary spots on neckline and hands.

Formulation: Emulsion cream containing 2% b-White™ + 1% Exo-T™

Application: Each product is applied on neckline and hands twice a day (morning & evening) Times measurement : T0, T+14 days, T+28 days, T+56 days Assessment criteria:

- Measurement of skin color (Spectrocolorimeter®)

- Scorage of the spots size and color by the technician

- Subjective evaluation

Clinical efficacy on neckline & hands spots

Scale for the size of spots

1 2 3 4 5 6 7 8 9 10

3 mm 1 cm

Scale for the intensity of spots color

- L* : measurement of the brightness or clarity: ↗ L* parameter = Lightening of the skin

- b*: measurement of blue-to-yellow spectrum: ↘ b* = ↘ in the yellow constituent of the skin

ITA° (individual Typological Angle) defines the skin pigmentation degree and includes L* & b*

When ↗↗ ITA parameter = decrease in skin pigmentation, increase in lightness

Results on hands

Results on neckline

The Flawless Duo induces sinificant skin lightening and improves skin tone rapidly!

Consumers appreciation

Tolerance Studies

Excellent Safety Profile

• HET CAM (concentration tested >20%)

• Acute skin tolerance (single patch test) (concentration tested >20 %)

• HRIPT (irritation and sensitization) (concentration tested > 20%)

• AMES Test (concentration tested > 20%)

• No UV-light absorbance (200 – 800 nm) – No risk of phototoxicity

Recommended dosage:

Intensive whitening: 2.5 - 5%

Corrective care & Age-spot: 1 – 2.5%

Lightening care & Skin illumination 0.5 – 1%

1% if combined with an exfoliant

Potential Applications:

INCI name: Water (1) (and) Butylene Glycol (2) (and) Hydrogenated Lecithin (3) (and)

Sodium Oleate (4) (and) Oligopeptide-68 (5) (and) Disodium EDTA (6)

• Whitening care

• Brightening care

• Age-spot treatment

• Anti-aging care

• Specific care: hands, armpits, décolleté

• Skin tone evenness

• Lightening foundation

• Photo-aging

• Ethnic skin care

Applications

Should be incorporated at the end of the manufacturing process, at a temperature of 35/40⁰C at pH6-8

To focus on…

Innovations – Performance – Safety

Summary

• β-White™: Innovative and unique whitening agent.

• Effective combination of a TGF-β agonist peptide encapsulated in a liposome.

• Unique regulatory action on the MITF pathway to decrease constitutive and facultative pigmentation!

• Better than Arbutin & Vit C

• Outstanding clinical results: 100% lightening effect

• Excellent safety profile.

Lucas Meyer Cosmetics’ whitening portfolio

Ingredient Origin In vitro Clinical

β-White™ Encapsulated Peptide

(TGF-β biomimetic)

- MITF, TRP 1, TRP2

- Tyrosinase

- Melanin synthesis

- Better efficacy on melanin synthesis than Arbutin & Vitamin C

- Reduction of dendricity & melanosome content

- ↑ Skin lightness by 1.9% after 28 day and +2.9% after 56 days.

- Skin color by 21% after 28 days and -30% after 56 days.

- Consumer test: Consumers found their skin tone more uniform & brigther

Tyrostat™ Plant extract

-Tyrosinase

- Better efficacy on tyrosinase inhibition than Arbutin, Tumeric and Hydroquinone

- Pigmentation (TAN & ERYTHEMA)

- Appearance of age-spots: -15% after 3 weeks & -25% after 6 weeks

-Consumer test with Melanostatine-5 on Asian skin

Melanostatine 5® Peptide

(α-MSH biomimetic)

- Tyrosinase

- Melanin synthesis

-Consumer test with Tyrostat on Asian skin

Exo-T™ Exopolysaccharide

- ↑ Desquamation & differentiation

THANK YOU!

2015-12-09