Control of redness & rosacea

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1 Control of redness & rosacea Temporary version

2 A 5 in 1 global control of inflammation to reduce skin redness and rosacea. Endothelyol is inspired by pharma to regulate all the key factors of redness and rosacea: Mechanical or infectious stress Internal deregulation downregulation of inflammation factors control of neovascularisation uniformization of skin tone improvement of rosacea in 28 days KERATINOCYTES IL8 and TNF-α secretion Cytokines release (pain and inflammation) PGE2 release Vasodilation (skin hyperreactivity) Endothelyol is a pure active ingredient obtained by enzymatic modification of natural plants hydroxybenzoic acid and hydroxycinnamic acids, by means of a proprietary biotechnology process. Redness and rosacea MASTOCYTES Histamine release Itching FIBROBLASTS VEGF production Neovascularisation

3 A 5 in 1 global control of inflammation to reduce skin redness and rosacea. Endothelyol is inspired by pharma to regulate all the key factors of redness and rosacea: downregulation of inflammation factors control of neovascularisation uniformization of skin tone improvement of rosacea in 28 days Endothelyol is a pure active ingredient obtained by enzymatic modification of natural plants hydroxybenzoic acid and hydroxycinnamic acids, by means of a proprietary biotechnology process. Mechanical or infectious stress Internal deregulation Endothelyol KERATINOCYTES IL8 and TNF-α secretion Cytokines release (pain and inflammation) PGE2 release Vasodilation (skin hyperreactivity) MASTOCYTES Histamine release Itching FIBROBLASTS VEGF production Neovascularisation

4 Tight control of redness factors (in vitro tests) Protocol: Endothelyol was tested for its ability to control redness factors. ELISA quantification of IL8 released was done on keratinocytes extracted from clinical human skin sample incubated with the product for 48h. IL8 (pg/ml/µg proteins) Interleukin 8 release control in IL-1β stimulated keratinocytes -67% p<.1 compared to stimulated control, Student s t Test Result: Endothelyol downregulates IL8 release by -67%. Control Induced (IL-1β) Endothelyol -.25% Endothelyol - 1% Endothelyol - 2.5%

5 Tight control of redness factors (in vitro tests) Protocol: Endothelyol was tested for its ability to control redness factors. ELISA quantification of TNFα released was done on keratinocytes extracted from clinical human skin sample incubated with the product for 48h. Result: Endothelyol downregulates TNF-α release by -39%. TNF-α release control in PMA stimulated keratinocytes TNF-α (pg/ml/µg proteins) Control Induced (PMA) Endothelyol -.25% Endothelyol - 1% Endothelyol - 1.5% p<.1 compared to stimulated control, Student s t Test -39%

6 Tight control of itching (in vitro tests) Protocol: Endothelyol was tested for its ability to control itching. ELISA quantification of histamine released was done on rodent mastocytes incubated with the product for 3 min. Result: Endothelyol downregulates histamine release by -19%. Histamine (ng/ml) Histamine release control in substance P stimulated mastocytes p<.1 compared to stimulated control, Student s t Test -19% Control Induced (Substance P) Endothelyol -.25% Endothelyol - 1%

7 Tight control of vasodilation (in vitro tests) Protocol: Endothelyol was tested for its ability to control vasodilation. ELISA quantification of PGE2 released was done on keratinocytes extracted from clinical human skin sample incubated with the product for 48h. PGE2 (pg/ml/µg proteins) Prostaglandin E2 release control in keratinocytes % Result: Endothelyol downregulates PGE2 release by -54%. Control Endothelyol -.1% Endothelyol -.25% Endothelyol - 1%

8 Reduction of neovascularisation (in vitro tests) Protocol: Endothelyol was tested for its ability to control neovascularisation. An ELISA quantification of the amont of VEGF released was done on keratinocytes extracted from clinical human skin sample incubated with the product for 48h. Result: Endothelyol reduces formation of new blood vessels by 46%. VEGF (pg/ml/µg proteins) Vascular Endothelyol Growth Factor release control in keratinocytes p<.5 compared to control, Student s t Test Control Endothelyol - 1% Endothelyol - 1.5% Endothelyol - 2.5% -46%

9 Inhibition of neo-vessels growth (ex vivo evaluation) Protocol: Endothelyol was tested for its anti-angiogenesis properties. A quantification of the number of neo-vessels created upon time was done on HskMEC (Microvascular endothelial human skin cells) cultured on MATRIGEL with or without the product for 17h. Number of pseudovessels Quantification of neo-vessels -1% Control Endothelyol % Endothelyol - 2.5% CONTROL' ENDOTHELYOL 2,5% Result: Endothelyol blocks neovessels growth. Dashed line : contour of a neo-vessel

10 Reduction of rosacea (clinical evaluation on skin under dermatological control) Protocol: A placebo and a cream containing 2% Endothelyol were tested in clinical study on 2 woman volunteers to evaluate the reduction of rosacea. The products were applied for 28 days, twice a day, on either half of the face. Day Day 28 Result: After 28 days, Endothelyol reduces rosacea by 7% to 12%. Endothelyol 2%

11 Increase in skin brightness (clinical evaluation on skin under dermatological control) Protocol: A placebo and a cream containing 2% Endothelyol were tested in clinical study on 2 women volunteers to evaluate the improvement of skin color. The products were applied for 28 days, twice a day, on either half of the face. Quantification of skin melanin content was done by Siascopy. Melanin content decrease (in %) Skin melanin content 2 Result: After 28 days, Endothelyol improves skin color: 11% of brightening. Placebo Endothelyol - 2%

12 Ecocert' TECHNICAL INFORMATION INCI: Origin: Preservation: Appearance: Solubility: Dosage: Processing: Intellectual property: Regulatory status: Claims: Ocular irritation: Skin irritation: Mutagenicity: Phototoxicity: Sensibilization: Glycerin, Rosmarinyl Glucoside, Caffeyl Glucoside, Gallyl Glucoside Biotech Preservative free Faint amber solution Water-soluble.25% - 2.5% Can be incorporated in any formula in liquid form at ph below 6.5 and temperature below 45 C Patented JP, KR, HK, AU, ASEAN, USA, CA, South-Am, Mid-East, EU Anti-rosacea, anti-redness, soothing SAFETY ASSESSMENT on NCTC L929 cells - low cytotoxicity at 1% OECD 439 assay - non irritant at 94.5% Single Patch Test - non irritant at 3% Ames assay - OECD non mutagenic OECD 432 assay - non phototoxic HRIPT assay - non sensitizing at 3% Registration pending

13 Thank you Induchem AG Industriestrasse 8A CH-864 Volketswil Induchem USA, Inc. 535 Fifth Avenue, Floor 23 New-York, NY117 Induchem France SAS 171 Bis Avenue Charles de Gaulle FR-922 Neuilly Sur Seine

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