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Rahul C. Mehta, Ph.D. Vice President, Research & Development

SkinMedica, An Allergan Company

SkinMedica:Bioengineering

Heritage and Future of Ground Breaking

Ingredients

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TNS®

Tissue Nutrient Solution

3

INCI Registered Cosmetic Ingredient:Human Fibroblast Conditioned Medium

Source: Neonatal foreskin fibroblasts cell bank• Single foreskin donation used to develop a cell banks

used for commercialization of multiple FDA-approved products

• TransCyte and Dermagraft wound-healing

• Cosmoderm and Cosmoplast facial fillers

Spent tissue culture medium used to grow fibroblast is collected and concentrated

What is TNS?

4

What makes TNS so valuable?

TNS Recovery Complex• 93.6% TNS

• Retail: $172 / 0.65 Oz

TNS Essential Serum• Side 1: 93.6% TNS

• Side 2: Antioxidant blend

• Retail: $ 270 / 1.0 Oz

Significant Revenue Contribution

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TNS Manufacturing Process

Growing Living Human Tissues

PolymerScience

BiochemistryCell Biology Bioengineering

Transplantation

TNS

6

Manufacturing of TNS

Cells from cell banks grow on a 3-dimentional scaffoldCollagen and extra-cellular matrix are produced Growth factors and other essential proteins are secreted into medium.

Growth factors levels are 4000 to 40000-fold higher than a 2-dimentional process

Secreted growth factors are concentrated and stabilized to make TNS

TNS

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Physiologically Balanced Composition

Optimal ratio and levels of fibroblast derived human growth factors for extracellular matrix production

At least 110 growth factors, cytokines and other active proteins identified

Mehta et al., J Drugs Dermatol, 7:864-871, 2008

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Stability of Growth Factors

ELISA assay shows that Growth Factors and Cytokines are present at high levels in TNS stored at room temperature for 24 months.

1

10

100

1000

10000

100000

3 10 12 14 24

Con

cent

ratio

n, p

g/m

L

Storage Time (months)

bFGF IL-6 VEGF

Mehta et al., J Drugs Dermatol, 7:864-871, 2008

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Collagen 1 and 3: Gene ExpressionEpiDerm-FT Human Skin Model

0

1

2

3

4

5

6

7

12 Hours 24 Hours

Col

lage

n 1

0

1

2

3

4

5

6

7

8

9

12 Hours 24 Hours

Col

lage

n 3

TNS0.05% Tretinoin

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Elsatin & Related Proteins: Gene ExpressionEpiDerm-FT Human Skin Model

-4

-2

0

2

4

6

8

10

12

14

12 Hours 24 Hours

Elas

tin

0

1

2

3

4

5

6

7

8

9

10

12 Hours 24 Hours

MA

GP-

1

TNS0.05% Tretinoin

0

1

2

3

4

5

6

12 Hours 24 HoursLO

X-1

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Hyaluronic Acid: Concentration in MediaEpiDerm-FT Human Skin Model

0

500

1000

1500

2000

2500

3000

3500

4000

12 Hours 24 Hours

TNS0.05% Tretinoin

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Effect of “Growth Factors” Products on Aging GenesEpiDerm-FT Human Skin Model

-3

-2

-1

0

1

2

3

4

TNSRecoveryComplex

NeocutisBioserum

ObagiRegenica

ZO SkinHealth

Ossential

JanMariniA. I. R.Booster

PrioriCellular

Recovery

PeauMagnifiqu

YouthRecruit

Fold

s C

hang

e ov

er C

ontro

l

COL1A1 COL3A1 ELN MAGP-1 LOXL-1 SOD1

1 = No ChangeLess Than 2 = No Significant Change

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Journal of Cosmeticand Laser Therapies

Fitzpatrick and Rostan4:25-34, 2003

Dermatologic Therapy Mehta and Fitzpatrick

20:350–359, 2007

Journal of Drugs in Dermatology

Mehta et al.7:864-871, 2008

Summary of Clinical Studies:TNS Recovery Complex

Statistically significant improvements in multiple photodamage parameters

Efficacy superior to placebo/vehicle and moisturizing skin care regimens

Superior in subjective and objective evaluations

Validated with positive structural changes in skin

Excellent patient satisfaction: 93% desire to continue use

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TNS® Increases Collagen Synthesis

-10%

0%

10%

20%

30%

40%

50%

60%

70%

3 Months(N=20)

6 Months(N=4)

% In

crea

se fr

om B

asel

ine

TNS Vehicle

p=0.004

Grenz Zone: Outermost dermal layer where new collagen synthesis

is first visible

Fitzpatrick RE, Rostan EF. Reversal of photodamage with topical growth factors: a pilot study. J Cosmet Laser Ther. 2003;5(1):25-34.

Sundaram H, Mehta RC, Norine JA, et al. Topically applied physiologically balanced growth factors: a new paradigm of skin rejuvenation. J Drugs Dermatol. 2009;8(5SupplSkinRejuvenation):4-13.

Thickness of Grenz Zone Collagen from BiopsyThickness of Grenz Zone Collagen from Biopsy

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Skin Surface Impression:Periorbital Area

Baseline

6 Months

Female Age 63

Female Age 52

Female Age 62

Mehta et al., J Drugs Dermatol, 7:864-871, 2008

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Provide all the necessary controlling functions for any given process instead of a single super-targeted functionConsistent with how biological processes work through use of multiple redundant pathways of achieving same end-pointReduces need for identifying individual “actives” provided quality control can be achieved by other meansSignificantly lower carbon foot-print as extensive purification is eliminated

Key Differentiating Benefit of Physiologically Balance Ingredients

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In place of introducing external compounds to mask the signs of skin aging, Biometa Essential Serum™ unlocks one’s own anti aging potential.

Biometa Complex™ has been shown to stimulate “key” proteins and genes within the skin that have been identified as being fundamental to the anti aging cascade; resulting in the improvement of all visible signs of aging

Biometa™ – Working with Skin’s Own Actives

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Using proprietary amino acids, proteins, vitamins and other key nutrients which induce a positive stress and metabolic energy to the Pichia to yield the ingredient; Biometa™ (Pichia pastorisferment filtrate).

MicrobePichia pastoris

Proprietary Growth Media

(Positive Stress)

Biometa™(trade name)

Pichia pastorisferment filtrate

(INCI name)

Biometa™(trade name)

Pichia pastorisferment filtrate

(INCI name)

BIOREACTOR

=

Starting Materials

Proprietary Bio-Fermentation

ProcessPichia pastoris fully

metabolizes New Material

New MaterialSynthesized

NEW Ingredient

=

What is Biometa™?

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Gene FunctionAQP3 Hydration

COL12A1, COL15A1, Col 1A1, etc Extracellular Matrix Proteins

TGF-BetaTIMP1 / TIMP3VEGFA / VEGFbFGF3PDGFRBIL10RB, IL11, IL8, etc.

Growth Factors and Cytokines involved in repair and ECM production

SOD1 AntioxidantHSP Anti-agingTJP1/ ZO-1 Skin Barrier

How Does it Work?

In vitro Gene Array: In cell culture, Biometa Complex modulates gene expression. Below are some of the key classes of genes that are up-regulated:

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SOD1 AQP1 AQP3 AQP5 TJP1 HSPB1

TGF-

Bet

a1

VE

GFB

FGF3

PD

GFR

B

TIM

P1

TIM

P3

MM

P3

MM

P12

MM

P19

Biometa: Key ECM Genes

Biometa: Other Key Genes

Gen

e E

xpre

ssio

n vs

. Unt

reat

ed C

ontro

l

Gen

e E

xpre

ssio

n vs

. Unt

reat

ed C

ontro

l MMP Genesdown-regulated

ECM Related Genesup-regulated

Key Anti-Aging Genesup-regulated

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Proprietary mixture shown to stimulate, express, and synthesize a number of “key” proteins (cytokines, growth factors, etc.) known to be involved in skin repair and remodeling including:

bFGF: Fibroblast Growth Factor

TIMP-1: Tissue Inhibitor of MetalloProteinases

VEGF: Vascular Endothelial Growth Factor

Protein Array confirms gene expression data

Induction of Key ECM Proteins

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Greater need for multifunctional holistic ingredients that can only be derived from natural sourcesFermentation with multiple micro-organism species to enhance “active’ contentPlant cell culture to improve supply stability and reduce environmental impact

What’s Next for SkinMedica?

2323

Thank You!