Reveal the Inner you

Regenerate Beauty through Collagen Stimulation

C 60

C 100

M 00

M 66

J 6

J 0

N 0

N 0

pantone 2985 C

pantone 286 C

2

Bone

reso

rptio

n

& rem

odeli

ng Fat loss

& redistribution

Dermal ageing

collagen lossM

uscle

tone

and at

rophy

• Facial muscles become more tensed and atrophic

• Contribute to facial sagging and droopiness

• Fat pads displacement

AGE

• Signifi cant loss of facial bone with age4

• Leads to biometric volume loss2-4

• Noticeable changes in the other layers of overlying soft tissue and skin1,3

• Fat pads loss and/or migration under muscular action leading to deep creases and contour defects1-6

• Accumulation of fat in some areas (e.g. under the lower eyelid, jaw, mouth) leading to the impression of permanent puffi ness

FACIAL AGEING PROCESS

BONE RESORPTION & REMODELLING

MUSCLE TONE & ATROPHY

FAT LOSS & REDISTRIBUTION

Facial ageing is a multifactorial process that affects different layers.

3

As the ageing skin loses its structural proteins (collagen and elastin), it becomes more lax and begins to sag, which contributes to a tired and aged look.

COLLAGEN MODIFICATIONS WITH AGEING

•Decrease in the level of collagen

• Changes in histological characteristics (collagen fi bres distribution)

• Changes in ultrastructure (collagen network disorganisation)

• Fragmentation of fi brils, fi broblast can no longer bind

COLLAGEN IN YOUTHFUL SKIN

DERMAL AGEING & COLLAGEN LOSS

COLLAGEN IN AGEING SKIN

CollagenProvides infrastructure forelastin and hyaluronic acid

ElastinHelps the skin retain its elasticity

Hyaluronic AcidWater binds to hyaluronic acid, keeping the skin moist

Well structured collagennetwork7

EPIDERMIS

DERMIS

SUBCUTANEOUSLAYER

Collagen networkdisorganisation7

DecreasedCollagen

DecreasedHyaluronic Acid

DecreasedElastin

EPIDERMIS

DERMIS

SUBCUTANEOUSLAYER

4

• Totally smooth polycaprolactone (PCL) microspheres 25-50 μm

• PBS*-based carboxymethylcellulose (CMC) gel-carrier

• Excellent safety profile and largely used in bioresorbable implants (sutures and orthopaedic implants dermal fillers, oral and maxillo-facial surgery) for several decades worldwide

• Used in numerous European (CE-certified) and US Food and Drug Administration (FDA) approved commercial bioresorbable products in cosmetic and pharmaceutical industries

Totally smooth polycaprolactone (PCL)

PCL microspheres homogenously suspended in a PBS*-based

carboxymethylcellulose CMC gel-carrier

STAT TM

Technology

Sustained Performance, Tunable Longevity and Total Bioresorbability

•Maintained correction over total duration of effect through one single injection •Different levels of action depending on patients' needs •Fully resorbable treatment with a predictable, controlled and tunable bioresorption and a high safety profile

PCL30% 70%

CMCGel carrier

PBS: Phosphate Buffered Saline

PCL & CMC

STATTM TECHNOLOGY: A unique manufacturing process with several benefits

THESE 3 FEATURES GIVE ELLANSÉTM UNIQUE ADVANTAGES

COMPOSITION

ELLANSÉTM: A TAILOR-MADE BIORESORBABLE COLLAGEN STIMULATOR8

5

ELLANSÉTM is an injectable implant, indicated for subdermal implantation in the face for the lasting correction of wrinkles and other facial ageing signs or conditions.

•Medical Device Class III8

•CE mark obtained in 2009 •Distributed in more than 80 countries

ELLANSÉTM comes in ready-to-use syringes: •2 x 1 ml syringes of ELLANSÉTM with 4 x 27G 3/4" needles •2 x 0.5 ml syringes of ELLANSÉTM with 4 x 27G 3/4" needles

ELLANSÉTM is available in 2 options -S and -M, that differ only in their duration of action. All the other product characteristics are identical for the entire product range.

CE MARK INDICATION

ELLANSÉTM: A TAILOR-MADE BIORESORBABLE COLLAGEN STIMULATOR8

6

MECHANISM OF ACTION9

2-in-1 actionImmediate fi lling

• CMC gel provides the immediate fi lling & wrinkle correction

Long-lasting volumisation through collagen stimulation

• PCL microspheres stimulate neocollagenesis

Before treatment When ELLANSÉTM is injected subcutaneously CMCgel provides immediate results

CMC gel is resorbed and PCL microspheres remain

PCL microspheres stimulate fi broblasts to produce new collagen

Overtime PCL microspheres are bioresorbed

Smooth and natural correction maintained throughout total duration of effect

1

3

5

2

4

6CMC: Carboxymethylcellulose; PCL: Polycaprolactone

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PREDICTABLE AND CONTROLLED TOTAL BIORESORBABILITY10-13

Thanks to state-of-the art STATTM Technology : • Initial length of the PCL chains is the uniquely distinguishing characteristic of ELLANSÉTM

• Varying the length of the PCL chains is the basis of the different levels of longevity options which differ from 1 to 2 years* that you can adapt to your patient needs and expectations

• Fully resorbable product via hydrolysis

* Expected longevity in-vivo based on extrapolation of clinical data from –S and –M and accepted PCL degradation behaviour.

PCL chainsPCL microspheres

MECHANISM OF ACTION9

MICROSPHERES SIZE: 25-50 μm for the whole range

ELLANSÉTM provides an effect of different durations from 1 to 2 years*.

At injection Chain Scission Total BioresorptionBioresorption

1 YearELLANSÉTM -S

At injection Chain Scission Total BioresorptionBioresorption

2 YearsELLANSÉTM -M

PCL: Polycaprolactone

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AREAS OF TREATMENT: ELLANSÉ™ RANGE

Sustained volumising capacity through collagen stimulation for natural and long-lasting results from 1 to 2 years*, ideal for volume restoration and contour defi nition.

Depth of InjectionELLANSÉTM is indicated for sub-dermal injections. For further injection techniques please refer to the ELLANSÉTM Injection Technique Guidelines (available upon request).Due to its cohesiveness, ELLANSÉTM is easy to shape and mold, enabling higher precision in the shaping and defi nition of treated areas.

Temples and Brow Area

Malar Augmentation Cheek

Cheek

Nasolabial Folds

Jaw Line

Nose Reshaping

Marionette Lines

Chin Defi nition

ELLANSÉTM

TREATMENT AREAS WHERE ELLANSÉTM -S and -M

NB: Glabella, lips, tear trough and eyelids are not recommended for the use of ELLANSÉTM

* Expected longevity in-vivo based on extrapolation of clinical data from –S and –M and accepted PCL degradation behaviour.

DERMIS

EPIDERMIS

SUB-DERMALTISSUE

PCL: Polycaprolactone

9

PROVEN NEOCOLLAGENESIS INDUCED BY ELLANSÉTM

13 months after ELLANSÉTM -M injection, PCL microspheres were surrounded with collagen deposition and a mild fi broblastic and histiocytic tissue response. Stainings were Haematoxylin & Eosin (A and B) and Martin-s Trichrome (C and D)

In rabbit tissue9

In human tissue14

ELLANSÉTM -M: 9 months post injection (rabbit) Haematoxylin & Eosin staining shows:Microspheres still round and intact during bioresorption processCollagen fi bres are stained red

ELLANSÉTM -M: 9 months post injection (rabbit) Picro Sirius Red (PSR), Polarised light shows:Red (arrows): collagen type IGreen (arrowheads): collagen type IIIConfi rmation of neocollagenesis

ELLANSÉTM -M: 21 months post injection (rabbit) Picro Sirius Staining, Polarised light shows :Red colour confi rming predominant presence of collagen type IType I collagen confi rms stable environment and long-term effi cacy

PCL: Polycaprolactone

10

ELLANSÉ™ offers clear advantages over the NASHA based dermal filler, both in terms of durability and efficiency15

PROVEN EFFICACY & SAFETY

High efficacy of ELLANSÉ™ - S and ELLANSÉ™ - M in nasolabial folds treatment with high safety over a 2 years period10

Investigator Evaluated Aesthetic Global Improvement Scale GAIS

Comparative clinical study of ELLANSÉ™ vs a NASHA hyaluronic acid for treatment of nasolabial folds15

Patie

nts

% w

ith Im

prov

emen

t

Patie

nts

% w

ith Im

prov

emen

t

ELLANSÉ™ -S

months months

3 6 9 12 15 18 24 3 6 9 12 15 18 24

ELLANSÉ™ -M

Of patients with at least improved results at 12 months

Improved Much Improved Very Much Improved

Of patients with at least improved results at 24 months

90%100%

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

35%

55%

10%

40% 45%

78%

11%

11%10%

20%

15%

20%10%

60%

45%

35%

45%

3,5%

51,7%

13,8%

62,8%

27,6%25,9%41,4%

50% 71%58%

50%

23%

77%

6%

44%31%

14%

7% 4%

5,2%

Improved Much Improved Very Much Improved

PCL: Polycaprolactone; HA: Hyaluronic acid

11

HIGH SAFETY PROFILE OF ELLANSÉ™

The unique smooth and spherical shape of ELLANSÉ™ microspheres :

• Is the basis for optimal biocompatibility as rough surfaces and irregular shaped microspheres have the propensity to induce adverse events, such as nodules, and result in decreased collagen deposition16-20

•Provide a safe, long-lasting and high quality tissue scaffold

SAFE PRODUCT COMPONENTS WITH A LONG SAFETY HISTORY

Perfectly Smooth

SEM Picture

Totally Spherical Microparticles

Light Microscopy Picture

High Quality Scaffold

Light Microscopy: Histology 2-weeks post intradermal injection

•Long-term and total bioresorption of ELLANSÉTM components through the normal metabolic pathways well documented

•PCL microspheres bioresorption demonstrated via radio-labeled bioresorption studies

of patients like to repeat ELLANSÉTM - S treatment

of patients like to repeat ELLANSÉTM - M treatment

•Total biocompatibility demonstrated via tests according to the ISO-10993 biocompatibility standard • 2-weeks implantation data clearly show the particles well-embedded in a healthy tissue environment and demonstrate excellent local tolerance

•In-house in-vitro resorption study of ELLANSÉTM Range PCL microspheres consistent with published literature data

SHORT-TERM SAFETY: Pre-Clinical Data7

IN-VITRO

LONG-TERM SAFETY: Scientific Evidence and Literature10, 13

HIGH PATIENT SATISFACTION10

ELLANSÉ™ -S & -M: Satisfaction using Visual Analogue Scale (VAS)15

75%

78%

At 24 months post-injection :Patient Satisfaction with ELLANSÉTM Treatment (mean)

Patient Satisfaction

Satisfaction 74% 81.7%

ELLANSÉTM- S12 Months

ELLANSÉTM- M24 Months

PCL: Polycaprolactone

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ELLANSÉ™ ABILITY TO REGENERATE BEAUTY

ELLANSÉ™ -S Nasolabial Folds

ELLANSÉ™ -S Nasolabial Folds

ELLANSÉ™ -M Nasolabial Folds

After 12 Months

Courtesy of Marion Moers-Carpi, MD, Germany

Before Treatment

Courtesy of Marion Moers-Carpi, MD, Germany

After 24 MonthsBefore Treatment

Courtesy of Marion Moers-Carpi, MD, Germany

After 12 MonthsBefore Treatment

13

Courtesy of Ayham Al-Ayoubi, MD, London, UK

Before Treatment After Treatment

Before Treatment After 3 Weeks

Courtesy of Dr. Fab Equizi, Liverpool, UK

Before Treatment After 2 Months

Courtesy of Alida Harb, MD, Riyadh, Saudi-Arabia

ELLANSÉ™ -M Nose Reshaping

ELLANSÉ™ -M Nasolabial Folds, Cheeks and Marionette Lines

ELLANSÉ™ -M Cheeks and Submalar Augmentation

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REFERENCES

1. Nicolau PJ, et al. Neocollagenesis after injection of a polycaprolactone based dermal fi ller in a rabbit. Eur J Aesth Med Dermatol 2013;3(1):19-26.

2. Moers-Carpi MM, et al. Polycaprolactone for the Correction of Nasolabial Folds: A 24-Month, Prospective, Randomized, Controlled Clinical Trial. Dermatol Surg 2013;39:457-463.

3. Murphy MR, et al. The ageing face consultation. In: Master Techniques in Facial Rejuvenation. Elsevier 2006;1-16.

4. Coleman SR, et al. The anatomy of the ageing face: volume loss and changes in 3-dimensional topography. Aesthet Surg J 2006;26(suppl 1):S4-S9.

5. Zimbler MS, et al. Anatomy and pathophysiology of facial ageing. Facial Plast Surg Clin North Am 2001;9:179-187.

6. Vleggaar D, et al. Dermatological implications of skeletal ageing: a focus on supraperiosteal volumization for perioral rejuvenation. J Drugs Dermatol 2008;7:209-220.

7. Le Louarn C. Botulinum toxin and the Face Recurve® concept: decreasing resting tone and muscular regeneration. Ann Chir Plast Esth 2007;52:165-176.

8. Donofrio LM. Fat distribution: a morphologic study of the ageing face. Dermatol Surg 2000;26:1107-1111.

9. Valenga Baroni, et al. Infl uence of ageing on the quality of the skin of white women- the role of collagen. Acta cirurgica Brasileira 2012; 27: 736-740

10. CE mark-Technical dossier (Whitepaper W113.05).

11. Pitt CG. Aliphatic polyesters II The degradation of Poly (DL-lactide), poly (ε-caprolactone), and their copolymers in vivo. Biomaterials 1981;2:215-220.

12. Varani J. Decrease collagen production in chronologically aged skin. Am J Pathol 2006;168: 1861-1868.

13. Woodruff MA, et al. The return of a forgotten polymer: polycaprolactone in the 21st century. Prog Polym Sci 2010;35(10):1217-1256.

14. Kim, et al. Neocollagenesis in human tissue injected with a polycaprolactone-based dermal fi ller. Journal of Cosmetic and Laser Therapy, 2014; Early Online: 1-3.

15. Galadari, et al. A randomized, prospective, blinded, split face, single center study comparing polycaprolactone to hyaluronic acid for treatment of nasolabial folds. The Journal of Cosmetic Dermatology.

16. Laeschke K. Biocompatibility of microparticles into soft tissue fi llers. Semin Cutan Med Surg 2004; 23(4):214-217.

17. Morhenn VB, et al. Phagocytosis of different particulate dermal fi ller substances by human macrophages and skin cells. Dermatol Surg 2002;28(6):484-490.

18. Anderson JM. Mechanism of infl ammation and infection with implanted devices. Cardiovasc Pathol 1993;2:33S-41S.

19. Matlage BF, et al. Tissue response to implanted polymers: The signifi cance of sample shape. J Biomed Meter Res 1976;10:391-397.

20. Nicolau PJ. Long-Lasting and permanent fi llers: Biomaterials infl uence over host response. Plast Reconstr Surg 2007;119:2271-2286.

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REFERENCES

B&

A C

AS

ES

SINCLAIR is a pharmaceutical company with a renowned strong skin expertise:

• Provides best in class treatments in aesthetics to further support physicians in

their practice thanks to unique treatments to answer all patient needs at all

ages through minimally invasive procedures.

• Is dedicated to offering safe and effective solutions to achieve optimal results

with limited downtime.

• SINCLAIR treatments respect skin's own natural processes and contribute to

maintain the skin in good condition and to rejuvenate the face at all ages.

SINCLAIR COMMITMENT

Unique products

portfolio based on

physician and

patient needs

High quality training

program based on

physician practice

and expectations

Create added value in your daily practice

Optimi e aesthetics outcome to increase

your patients satisfaction

s

16

Reveal the Inner you

Easy to inject Immediate correction Sustained volumising capacity

through collagen stimulation9 Maintained correction

over total duration of effect

Easy to hold Long-lasting effect from 1 to 2 years*

Natural results from patients own collagen stimulation

High level of patient satisfaction10

* Expected longevity in-vivo based on extrapolation of clinical data from –S and –M and accepted Polycaprolactone (PCL) degradation behaviour.

Genop Healthcare (Pty) Ltd. PO Box 3911, Halfway House, 1685, South Africa.Co. Reg.No.: 1984/011575/07. www.genop.co.za. 02/2016/NS/60.