A SYNTHETIC PENTAPEPTIDE: Palmitoyl-Lys-Thr-Thr-Lys-Ser Replica of a type I procollagen fragment

Pal-KTTKS: Biological Activity Stimulation in vitro (fibroblasts) of Collagen I, III and Fibronectin synthesis (Katayama et al. 1993) Stimulation of Collagen IV on aged fibroblasts (Sederma/Bioalternatives, 1999) Collagen stimulation proven using biopsies (Sederma/Biopredic 1998)

In vitro efficacy tests on human fibroblast culture

Ex vivo efficacy test on human skin biopsies (1000 ppm)

In vivo efficacy test Wrinkle surface Parameter: % of surface (yellow zone) occupied with deep wrinkles (> 200µm) Wrinkle volume Parameter: volume of one of the main wrinkles (mm³) Surface accidents Parameter: roughness (skin smoothing)

In vivo efficacy test Cream with 3% Matrixyl / 2 applications a day during 6 months / 25 panelists / hemifacial application / analysis of eye contour wrinkles Wrinkles are visually less pronounced. Skin is smoother. In the scope of autoevaluation, these results have been confirmed by the panelists. -68% -24% -16%

In vivo efficacy test against a cream containing 5% Vitamin C Cream with 3% Matrixyl / Cream with 5% Vitamin C / 2 applications a day during 6 months / 10 panelists / hemifacial application / analysis of eye contour wrinkles 1. Wrinkle density 2. % surface of wrinkles >200µm 3. Roughness 4. Volume of one of the main wrinkles 5. Mean depth of one of the main wrinkles

Before treatmentAfter treatment In vivo claim substantiation: results

Before treatmentAfter treatment

PROTOCOL Cream containing Matrixyl TM 3% versus Cream containing Retinol 0.07% (best ratio tolerance/efficacy according to publication) (Stability control of Retinol every month) Daily application during the first 2 months, twice daily applications for the following 2 months / 16 volunteers In vivo study of Matrixyl TM antiwrinkle activity versus Retinol DIGITAL-IMAGE ANALYSIS DERMATOLOGICAL EVALUATION ECHOGRAPHY

DIGITAL-IMAGE ANALYSIS After a 4 months treatment, Matrixyl TM improves significantly cutaneous relief. Matrixyl TM acts as effectively as retinol, differences between the two products are not significant. MATRIXYL  RETINOL Mean of wrinkles depth Mean of wrinkles length Volume of the main wrinkle Mean of wrinkles surface Mean of wrinkles depth Mean of wrinkles length Mean of wrinkles surface Volume of the main wrinkle

DERMATOLOGICAL EVALUATION After 4 months, the dermatologist observed a significant decrease of wrinkles intensity with both products. Matrixyl TM efficacy is comparable to retinol. ON WRINKLES MATRIXYL  RETINOL Forehead PeriorbitalNasogenian groove Forehead PeriorbitalNasogenian groove

ECHOGRAPHY Echographic measurements on temples show that Matrixyl  acts significantly on skin thickness. Measurements of the improvement of skin thickness on temples at 2 and 4 months / T0 Retinol Matrixyl  2 months 4 months 2 months

T0 4 MONTHS

T0

New results presented at the International Dermatological Congress (Paris, 2002) Redensifying skin

Protocol 2 groups of 30 volunteers: 1 group treated during 4 months with a cream containing 5% Matrixyl 1 group treated during 4 months with a cream containing Matrixyl’s excipient Treated areas: face and neck Biopsies at T 0, T 2 months and T 4 months in the sub-maxillar zone Assessment of elastin and collagen 4 Impressions: Measurement of main wrinkle volume Measurement of mean wrinkle depth Assessment of roughness Methods:

Results Stimulation of elastin ElastinCollagen IV (DEJ) Matrixyl Visible increase in density and size of fibres Regular distribution ExcipientNo increase or decrease (except for 2 volunteers) Irregular distribution T0T2 monthsT4 months Volunteers treated with Matrixyl Volunteers treated with excipient Stimulation of elastin after 2 months, confirmed after 4 months Increase in thickness of cutaneous tissue

Results Increase in collagen IV synthesis Restructuration of dermo- epidermal junction ControlMatrixylExcipient Collagen IV: results after 4 months

Results: cutaneous relief 2 months MatrixylPlacebo 4 months -24.4% -26.8% % of variation with respect to T % After 4 months of treatment, the average depth of wrinkles decreased by 27% Wrinkle depth after 2 and 4 months

36% The volume of the main wrinkle decreased by 36% after 4 months No significant result was achieved with the placebo Determination of main wrinkle volume 2 months MatrixylPlacebo 4 months -35.8% -36.8% % of variation with respect to T Results: cutaneous relief

13% After 4 months of treatment, skin’s roughness decreased by 13% Skin is smoother Effect on cutaneous microrelief 2 mois MatrixylPlacebo 4 mois -9.1% -12.8% % of variation with respect to T Results: cutaneous relief

Conclusion Matrixyl is an anti-ageing peptide with substantiated efficacy in antiwrinkle treatment. It acts against several causes of ageing: Consumer benefit is multiple:  Less wrinkles  A brighter, smoother skin  Increase in skin density In vitro In vivo On human biopsies (ex vivo)  Stimulation of collagen IV, GAG, collagen I and II  vs vitamin C  vs retinol  Stimulation of elastin and collagen IV