EPIGENIST The epidermal rejuvenator. by Beauty Creations another Care Creations product group Inspired by Life

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1 EPIGENIST The epidermal rejuvenator by Beauty Creations another Care Creations product group Inspired by Life

2 2 EPIGENIST A redensified and thicker epidermis in 8 weeks EPIGENIST A restructured and thicker epidermis in 8 weeks How can one maintain a natural, youthful appearance? One of the main beauty secrets is to keep the first shield of our body healthy: our epidermis. A young epidermis is dense, thick and its major components are continuously regenerated. This relatively fast process keeps those cells plump and results in youthful and healthy looking skin on the surface. In the frame of research performed on epidermal aging, BASF Beauty Creations investigated the role of skin innervation and made a surprising discovery. We observed that when the skin is no longer innervated, the epidermis loses its volume to reach the appearance of aged skin. Could this cutaneous aging be explained partially by the decrease of innervation? The scientific results highlight the major influence of nerve fibers on the formation of a thick and well organized epidermis, characteristic of beautiful, young skin. Having close contact with keratinocytes, nerve endings can influence their proliferation, differentiation, and survival, directly impacting epidermal organization. With age, innervation within the epidermis decreases and this depletion causes epidermal thinning. BASF Beauty Creations thus looked for an innovative way to address the issue of epidermal thinning due to lack of innervation. Thanks to major advances made within our laboratories, we are now able to reverse time through the science of neuritogenesis: the power to regenerate nerve fibers. Our innovation, EPIGENIST shows the ability to boost neuritogenesis in the epidermis. When applied on the skin, EPIGENIST reverses the natural degradation of nerve fibers and their growth restarts, counterbalancing time passing by. Reinnervated, the epidermis reclaims the quality of its youth: less senescent cells, a proper organization, and visibly thicker, healthier skin. While our epidermis is reboosted from the inside, this directly impacts the appearance on the outside: the skin is smoothed and gains back its brightness. The rejuvenated skin no longer betrays our age. Cosmetic use Daily anti-ageing treatment Anti-dull skin Fine wrinkles treatment Cosmetic properties Increases skin innervation by boosting neuritogenesis Improves cells longevity Increases epidermal thickness Increase epidermal cohesion and quality

3 In vitro efficacy 3 In vitro efficacy EPIGENIST, the power to reverse time through neuritogenesis Proven effect of EPIGENIST on neuritogenesis Our aim To demonstrate the ability of EPIGENIST to boost neuritogenesis. PC12 (nerves cells) cells were seeded in a medium where EPIGENIST was added after 24 hours of incubation at 0.005% and 0.025% (fig. 1). Figure 1: Image of PC12 cells culture before treatment. Neurites length (pixels) Figure 2: Image of PC12 cells culture after 5 days of incubation with EPIGENIST at 0.025%. Results The addition of EPIGENIST at 0.005% and 0.025% in the culture for 5 days has significantly increased the length of the PC12 neurites compared to untreated control culture (fig. 2, neurites colored in red). Statistics Conclusion Presence of EPIGENIST at 0.005% and 0.025% in the culture medium clearly increased, in a dose dependent manner, the length of the PC12 dendrite (fig. 3). EPIGENIST is able to boost neuritogenesis. Proven rejuvenation effect of EPIGENIST on re-innervated human skin model Mean ± SEM of 2 assays U test of Mann-Whitney (**) p < 0.01 Figure 3: Effect of EPIGENIST on neurites length versus untreated control in a model of cultured PC12 cells. Innovation from BASF Beauty Creations: we developed a new model of reinnervated human skin to demonstrate the rejuvenation power of our ingredient. This model was built from skin explant co-cultured with primary sensory neurons (PSN) (Study report upon request). Rejuvenation effect through the increase of cells longevity Figure 4: Re-innervated skin model Green staining of apoptotic cells. Figure 5: Re-innervated skin model + EPIGENIST at 0.025% Green staining of apoptotic cells. When EPIGENIST is added the epidermal cells survival is significantly improved (fig. 4, fig. 5). -39% of apoptotic cells with EPIGENIST * * Complementary tests, comprehensive results and detailed protocol are available within the scientific brochure.

4 4 In vitro efficacy In vitro efficacy Rejuvenation effect through the increase of epidermis thickness Due to its properties to boost innervation, EPIGENIST clearly improves epidermal thickness and quality. It helps rejuvenate the skin (fig. 6, fig. 7). + 28% of epidermal thickness with EPIGENIST * Figure 6: Re-innervated skin model Visualization of epidermal living layers by desmoplakin 1 immunostaining (in green). Figure 7: Re-innervated skin + EPIGENIST at 0.025% Visualization of epidermal living layers by desmoplakin 1 immunostaining (in green). Rejuvenation effect through the increase of cells proliferation When the innervation is boosted by the addition of EPIGENIST, the proliferation index (number of Ki67 positive cells for 100 µm of dermal-epidermal junction (DEJ) length) drastically increases in the skin. The cells gained back their ability to proliferate to create new skin layers. The epidermis is rejuvenated (fig. 8). + 25% of improvement of cellular proliferation with EPIGENIST * A Figure 8: Visualization of Ki67, markers of proliferation in A) Re-innervated skin model and B) re-innervated skin with EPIGENIST at 0.025%. B * Complementary tests, comprehensive results and detailed protocol are available within the scientific brochure. EPIGENIST boosts neuritogenesis. EPIGENIST is able to rejuvenate aged skin and makes it visibly appear younger: the longevity of cells is increased; the epidermis is thicker and better organized; the proliferation of cells is increased. With EPIGENIST, time is reversed and the epidermis returns to a young, healthy appearance.

5 In vivo studies 5 In vivo studies Thickness (D56 - D0) (µm) EPIGENIST, the power to visibly bring back the youth of your skin in 8 weeks Statistics Mean ± SEM of 20 volunteers Student s t test Clinical tests conducted on a panel of 20 female human volunteers aged from 45 to 55 yo. EPIGENIST is formulated in emulsion at 0.5% applied twice a day on hemi-face for 8 weeks. EPIGENIST at 0.5% Placebo Our aim To demonstrate the ability of EPIGENIST at 0.5% to increase the epidermal thickness, and visibly improve the skin radiance and roughness. Figure 9: Difference in epidermal thickness after 56 days of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline. Results on epidermal thickness After 8 weeks of treatment with 0.5% of EPIGENIST the thickness of the epidermis is increased by 10% while no evolution was obtained with the placebo (fig. 9, fig. 10). Conclusion After 8 weeks of treatment, EPIGENIST shows a clear efficacy on epidermis thickness and aspect improvement. EPIGENIST contributes to epidermal thickness improvement by 10% in 8 weeks. Figure 10: Pictures of epidermal thickness before and after 8 weeks of treatment by EPIGENIST at 0.5% (confocal microscopy). Luminosity Radiance Results on skin radiance The measurement of the skin luminosity and radiance was done on hemi-face, treated with placebo or EPIGENIST, before and after 8 weeks of treatment. After 8 weeks of treatment by EPIGENIST at 0.5% on the hemi-face, a positive and significant increase of both luminosity and radiance parameters was observed compared to the hemi-face treated by the placebo (fig. 11).* Statistics After 8 weeks with EPIGENIST : better skin complexion and visibly brighter skin. Mean ± SEM Student t test (two-tailed) NS not significant (****) p < (***) p < (**) p < 0.01 EPIGENIST at 0.5% Placebo * Complementary results, face pictures available in the scientific brochure Figure 11: Evolution of the luminosity and skin radiance after 8 weeks of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline.

6 6 In vivo studies In vivo studies Results on skin roughness The skin roughness parameters were evaluated by topography analysis of the data obtained by fringe projection at the level of the crow s feet. The considered parameters were: Stm (Mean difference between peaks and valleys) and SA (Average roughness). Stm μm SA μm A significant decrease of roughness parameters was observed after treatment of the hemi-face by EPIGENIST at 0.5% compared to the hemi-face treated by the placebo (fig. 12). Statistics Student t test (two-tailed) ( ) p < 0.1 NS not significant EPIGENIST at 0.5% Placebo The fine wrinkles are visibly reduced, the skin is smoothed (fig. 13). After 8 weeks with EPIGENIST : the skin surface is smoothed and the wrinkles are reduced comparatively to placebo treatment. Figure 12: Difference in the skin roughness parameters after 8 weeks of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline. EPIGENIST Placebo Figure 13: Illustration of the smoothing effect of EPIGENIST after 8 weeks of treatment. Conclusion EPIGENIST has reversed the time through its power to regenerate nerve fibers: it has rejuvenated the epidermis by increasing epidermal thickness, The skin is visibly smoothed and less dull. With EPIGENIST the skin looks more youthful and radiant.

7 Origin / Description 7 EPIGENIST Origin / Description Voandzeia subterranea ground peas With the idea to find an ingredient with a rejuvenation power, BASF went look in the deep nature of indigenous African lands. There grows a pea with an intriguing property: the bambara pea. Cultivated for its nutritional qualities (rich in proteins, vitamins, and mineral salts), this pea also brings benefit on soil fertility. Beyond those properties, Voandzeia subterranea proved us its great contribution for our skin wellbeing. We extracted this power to build our new rejuvenating active ingredient. Summary file EPIGENIST PW LS10003 Regulatory Data INCI: Voandzeia subterranea seed extract (and) Maltodextrin China: Each component listed in International Cosmetic Ingredient Standard Chinese name (2007 & 2010 versions) and IECIC (2014 version) CAS#: (Naturally occurring substance); EINECS#: ; Appearance White to light beige powder with a characteristic odor Preservative None Formulation Data Concentration of use: 0.5% Solubility: Soluble in water Incorporation method: EPIGENIST must be dissolved into 4 times its weight of water at room temperature and then incorporated into the cosmetic product below 40 C, during the finished process. Optimal ph: Storage In its original packaging and protected from moisture, at C Shelf Life 24 months Patent family EP B1, FR B1, US B Natural Labels None

8 Europe North America South America Asia Pacific BASF East Asia Personal Care 45/F Jardine House No.1 Connaught Place Central, Hong Kong BASF Personal Care and Nutrition GmbH HCC - CM Monheim am Rhein Germany BASF Corporation North American Regional Headquarters 100 Park Avenue Florham Park, NJ USA BASF S.A. Av. das Nações Unidas, Crystal Tower São Paulo - SP Brazil Phone: +33 (0) Phone: Phone: Phone: Publisher BASF Beauty Care Solutions France SAS 3, Rue de Seichamps Pulnoy (France) Pictures BASF Beauty Care Solutions France SAS. All rights reserved. / Registered trademark / trademark of BASF in several countries Global Edition, September 2014 Although all statements and information in this publication are believed to be accurate and reliable, they are presented gratis and for guidance only, and risks and liability for results obtained by use of the products or application of the suggestions described are assumed by the user. SELLER MAKES NO WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, BY FACT OR LAW, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Statements or suggestions concerning possible use of the products are made without representation or warranty that any such use is free of patent infringement and are not recommendations to infringe any patent. The user should not assume that toxicity data and safety measures are indicated or that other measures may not be required. The claims and supporting data provided in this publication have not been evaluated for compliance with any jurisdiction s regulatory requirements and the results reported may not be generally true under other conditions or in other matrices. Users must evaluate what claims and information are appropriate and comply with a jurisdiction s regulatory requirements. Recipient of this publication agrees to (1) indemnify and hold harmless each entity of the BASF organization for any and all regulatory action arising from recipient s use of any claims or information in this publication, including, but not limited to, use in advertising and finished product label claims, and (2) not present this publication as evidence of finished product claim substantiation to any regulatory authority.

9 EPIGENIST The epidermal rejuvenator by Beauty Creations another Care Creations product group Inspired by Life

10 2 EPIGENIST A redensified and thicker epidermis in 8 weeks EPIGENIST A restructured and thicker epidermis in 8 weeks How can one maintain a natural, youthful appearance? One of the main beauty secrets is to keep the first shield of our body healthy: our epidermis. A young epidermis is dense, thick and its major components are continuously regenerated. This relatively fast process keeps those cells plump and results in youthful and healthy looking skin on the surface. In the frame of research performed on epidermal aging, BASF Beauty Creations investigated the role of skin innervation and made a surprising discovery. We observed that when the skin is no longer innervated, the epidermis loses its volume to reach the appearance of aged skin. Could this cutaneous aging be explained partially by the decrease of innervation? The scientific results highlight the major influence of nerve fibers on the formation of a thick and well organized epidermis, characteristic of beautiful, young skin. Having close contact with keratinocytes, nerve endings can influence their proliferation, differentiation, and survival, directly impacting epidermal organization. With age, innervation within the epidermis decreases and this depletion causes epidermal thinning. BASF Beauty Creations thus looked for an innovative way to address the issue of epidermal thinning due to lack of innervation. Thanks to major advances made within our laboratories, we are now able to reverse time through the science of neuritogenesis: the power to regenerate nerve fibers. Our innovation, EPIGENIST shows the ability to boost neuritogenesis in the epidermis. When applied on the skin, EPIGENIST reverses the natural degradation of nerve fibers and their growth restarts, counterbalancing time passing by. Reinnervated, the epidermis reclaims the quality of its youth: less senescent cells, a proper organization, and visibly thicker, healthier skin. While our epidermis is reboosted from the inside, this directly impacts the appearance on the outside: the skin is smoothed and gains back its brightness. The rejuvenated skin no longer betrays our age. Cosmetic use Daily anti-ageing treatment Anti-dull skin Fine wrinkles treatment Cosmetic properties Increases skin innervation by boosting neuritogenesis Improves cells longevity Increases epidermal thickness Increase epidermal cohesion and quality

11 In vitro efficacy 3 In vitro efficacy EPIGENIST, the power to reverse time through neuritogenesis Proven effect of EPIGENIST on neuritogenesis Our aim To demonstrate the ability of EPIGENIST to boost neuritogenesis. PC12 (nerves cells) cells were seeded in a medium where EPIGENIST was added after 24 hours of incubation at 0.005% and 0.025% (fig. 1). Figure 1: Image of PC12 cells culture before treatment. Neurites length (pixels) Figure 2: Image of PC12 cells culture after 5 days of incubation with EPIGENIST at 0.025%. Results The addition of EPIGENIST at 0.005% and 0.025% in the culture for 5 days has significantly increased the length of the PC12 neurites compared to untreated control culture (fig. 2, neurites colored in red). Statistics Conclusion Presence of EPIGENIST at 0.005% and 0.025% in the culture medium clearly increased, in a dose dependent manner, the length of the PC12 dendrite (fig. 3). EPIGENIST is able to boost neuritogenesis. Proven rejuvenation effect of EPIGENIST on re-innervated human skin model Mean ± SEM of 2 assays U test of Mann-Whitney (**) p < 0.01 Figure 3: Effect of EPIGENIST on neurites length versus untreated control in a model of cultured PC12 cells. Innovation from BASF Beauty Creations: we developed a new model of reinnervated human skin to demonstrate the rejuvenation power of our ingredient. This model was built from skin explant co-cultured with primary sensory neurons (PSN) (Study report upon request). Rejuvenation effect through the increase of cells longevity Figure 4: Re-innervated skin model Green staining of apoptotic cells. Figure 5: Re-innervated skin model + EPIGENIST at 0.025% Green staining of apoptotic cells. When EPIGENIST is added the epidermal cells survival is significantly improved (fig. 4, fig. 5). -39% of apoptotic cells with EPIGENIST * * Complementary tests, comprehensive results and detailed protocol are available within the scientific brochure.

12 4 In vitro efficacy In vitro efficacy Rejuvenation effect through the increase of epidermis thickness Due to its properties to boost innervation, EPIGENIST clearly improves epidermal thickness and quality. It helps rejuvenate the skin (fig. 6, fig. 7). + 28% of epidermal thickness with EPIGENIST * Figure 6: Re-innervated skin model Visualization of epidermal living layers by desmoplakin 1 immunostaining (in green). Figure 7: Re-innervated skin + EPIGENIST at 0.025% Visualization of epidermal living layers by desmoplakin 1 immunostaining (in green). Rejuvenation effect through the increase of cells proliferation When the innervation is boosted by the addition of EPIGENIST, the proliferation index (number of Ki67 positive cells for 100 µm of dermal-epidermal junction (DEJ) length) drastically increases in the skin. The cells gained back their ability to proliferate to create new skin layers. The epidermis is rejuvenated (fig. 8). + 25% of improvement of cellular proliferation with EPIGENIST * A Figure 8: Visualization of Ki67, markers of proliferation in A) Re-innervated skin model and B) re-innervated skin with EPIGENIST at 0.025%. B * Complementary tests, comprehensive results and detailed protocol are available within the scientific brochure. EPIGENIST boosts neuritogenesis. EPIGENIST is able to rejuvenate aged skin and makes it visibly appear younger: the longevity of cells is increased; the epidermis is thicker and better organized; the proliferation of cells is increased. With EPIGENIST, time is reversed and the epidermis returns to a young, healthy appearance.

13 In vivo studies 5 In vivo studies Thickness (D56 - D0) (µm) EPIGENIST, the power to visibly bring back the youth of your skin in 8 weeks Statistics Mean ± SEM of 20 volunteers Student s t test Clinical tests conducted on a panel of 20 female human volunteers aged from 45 to 55 yo. EPIGENIST is formulated in emulsion at 0.5% applied twice a day on hemi-face for 8 weeks. EPIGENIST at 0.5% Placebo Our aim To demonstrate the ability of EPIGENIST at 0.5% to increase the epidermal thickness, and visibly improve the skin radiance and roughness. Figure 9: Difference in epidermal thickness after 56 days of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline. Results on epidermal thickness After 8 weeks of treatment with 0.5% of EPIGENIST the thickness of the epidermis is increased by 10% while no evolution was obtained with the placebo (fig. 9, fig. 10). Conclusion After 8 weeks of treatment, EPIGENIST shows a clear efficacy on epidermis thickness and aspect improvement. EPIGENIST contributes to epidermal thickness improvement by 10% in 8 weeks. Figure 10: Pictures of epidermal thickness before and after 8 weeks of treatment by EPIGENIST at 0.5% (confocal microscopy). Luminosity Radiance Results on skin radiance The measurement of the skin luminosity and radiance was done on hemi-face, treated with placebo or EPIGENIST, before and after 8 weeks of treatment. After 8 weeks of treatment by EPIGENIST at 0.5% on the hemi-face, a positive and significant increase of both luminosity and radiance parameters was observed compared to the hemi-face treated by the placebo (fig. 11).* Statistics After 8 weeks with EPIGENIST : better skin complexion and visibly brighter skin. Mean ± SEM Student t test (two-tailed) NS not significant (****) p < (***) p < (**) p < 0.01 EPIGENIST at 0.5% Placebo * Complementary results, face pictures available in the scientific brochure Figure 11: Evolution of the luminosity and skin radiance after 8 weeks of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline.

14 6 In vivo studies In vivo studies Results on skin roughness The skin roughness parameters were evaluated by topography analysis of the data obtained by fringe projection at the level of the crow s feet. The considered parameters were: Stm (Mean difference between peaks and valleys) and SA (Average roughness). Stm μm SA μm A significant decrease of roughness parameters was observed after treatment of the hemi-face by EPIGENIST at 0.5% compared to the hemi-face treated by the placebo (fig. 12). Statistics Student t test (two-tailed) ( ) p < 0.1 NS not significant EPIGENIST at 0.5% Placebo The fine wrinkles are visibly reduced, the skin is smoothed (fig. 13). After 8 weeks with EPIGENIST : the skin surface is smoothed and the wrinkles are reduced comparatively to placebo treatment. Figure 12: Difference in the skin roughness parameters after 8 weeks of treatment with an emulsion with EPIGENIST at 0.5% & emulsion placebo, comparatively to baseline. EPIGENIST Placebo Figure 13: Illustration of the smoothing effect of EPIGENIST after 8 weeks of treatment. Conclusion EPIGENIST has reversed the time through its power to regenerate nerve fibers: it has rejuvenated the epidermis by increasing epidermal thickness, The skin is visibly smoothed and less dull. With EPIGENIST the skin looks more youthful and radiant.

15 Origin / Description 7 EPIGENIST Origin / Description Voandzeia subterranea ground peas With the idea to find an ingredient with a rejuvenation power, BASF went look in the deep nature of indigenous African lands. There grows a pea with an intriguing property: the bambara pea. Cultivated for its nutritional qualities (rich in proteins, vitamins, and mineral salts), this pea also brings benefit on soil fertility. Beyond those properties, Voandzeia subterranea proved us its great contribution for our skin wellbeing. We extracted this power to build our new rejuvenating active ingredient. Summary file EPIGENIST PW LS10003 Regulatory Data INCI: Voandzeia subterranea seed extract (and) Maltodextrin China: Each component listed in International Cosmetic Ingredient Standard Chinese name (2007 & 2010 versions) and IECIC (2014 version) CAS#: (Naturally occurring substance); EINECS#: ; Appearance White to light beige powder with a characteristic odor Preservative None Formulation Data Concentration of use: 0.5% Solubility: Soluble in water Incorporation method: EPIGENIST must be dissolved into 4 times its weight of water at room temperature and then incorporated into the cosmetic product below 40 C, during the finished process. Optimal ph: Storage In its original packaging and protected from moisture, at C Shelf Life 24 months Patent family EP B1, FR B1, US B Natural Labels None

16 Europe North America South America Asia Pacific BASF East Asia Personal Care 45/F Jardine House No.1 Connaught Place Central, Hong Kong BASF Personal Care and Nutrition GmbH HCC - CM Monheim am Rhein Germany BASF Corporation North American Regional Headquarters 100 Park Avenue Florham Park, NJ USA BASF S.A. Av. das Nações Unidas, Crystal Tower São Paulo - SP Brazil Phone: +33 (0) Phone: Phone: Phone: Publisher BASF Beauty Care Solutions France SAS 3, Rue de Seichamps Pulnoy (France) Pictures BASF Beauty Care Solutions France SAS. All rights reserved. / Registered trademark / trademark of BASF in several countries Global Edition, September 2014 Although all statements and information in this publication are believed to be accurate and reliable, they are presented gratis and for guidance only, and risks and liability for results obtained by use of the products or application of the suggestions described are assumed by the user. SELLER MAKES NO WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, BY FACT OR LAW, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Statements or suggestions concerning possible use of the products are made without representation or warranty that any such use is free of patent infringement and are not recommendations to infringe any patent. The user should not assume that toxicity data and safety measures are indicated or that other measures may not be required. The claims and supporting data provided in this publication have not been evaluated for compliance with any jurisdiction s regulatory requirements and the results reported may not be generally true under other conditions or in other matrices. Users must evaluate what claims and information are appropriate and comply with a jurisdiction s regulatory requirements. Recipient of this publication agrees to (1) indemnify and hold harmless each entity of the BASF organization for any and all regulatory action arising from recipient s use of any claims or information in this publication, including, but not limited to, use in advertising and finished product label claims, and (2) not present this publication as evidence of finished product claim substantiation to any regulatory authority.

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