IN VIVO TEST: ANALYSIS OF SKIN SURFACE DEPRESSIONS IN VIVO TEST: ANALYSIS OF SKIN GRAIN AND SOFTNESS IN VIVO TEST: ANALYSIS OF SKIN GRAIN AND SOFTNESS

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1 NEW SKIN INTENSIVE FACE SERUM CLINICAL STUDIES CORNEOSTICKER DS Multifunctional Skin Perfecting Dressing ANATOMICAL & PHYSIOLOGICAL DRESSING CORNEOSTICKER DS IS THE CORNEOCYTE OF THE CORNEOCYTE WHAT IS IT? Opposite photo on the top allows the visualization of the pentagonal shape of corneocytes at the surface of a human skin explant. Below, after application of CORNEOSTICKER DS, corneocytes are no more visible, they have been totally recovered by the smaller corneocyte like of CORNEOSTICKER DS. New tool for Corneotherapy, CORNEOSTICKER DS is an active dressing that mimics the CorneoSphere (corneocyte + its environment) to renovate and perfect skin surface. WHAT IS IT DEVELOPED TO DO? Its innovative helix structure opens on skin surface to instantly blur and smooth skin grain while providing biomolecules that work to restructure the epidermis in depth. After 2 weeks use, the skin is smoother, softer, more luminous and flawless. CORNEOSTICKER DS is physically opened on the surface of the skin, on and between the altered corneocytes, to form a second anatomical skin which protects the surface of the stratum corneum. Photonic microscopy of the surface of a skin explant. CORNEOSTICKER DS A CORNEOSPHERE TO REVOLUTIONIZE CORNEOTHERAPY CORNEOSTICKER DS is made up of a large number of mineral sheets which open up in the shape of a helix. Once opened, the sheets reveal a combination of components which make up the corneocyte environment in the stratum corneum: Minerals to boost the NMF (concentrated seawater) Lactates Lipids to strengthen lipidic cement (sebum like) Amino acids to boost the NMF (microalga) Each object mimics a corneocyte with its own environment. Photonic microscopy of the surface of a skin explant after aplication of CORNEOSTICKER DS. A STRUCTURE THAT OPEN to deploy a second skin on the surface of stratum corneum A STRUCTURE THAT OPEN to deploy a second skin on the surface of stratum corneum A STRUCTURE THAT OPEN to deploy a second skin on the surface of stratum corneum A STRUCTURE THAT OPEN to deploy a second skin on Whenthe applied epidermis, surfaceto ofthe stratum corneum Corneosticker DS forms a second skin that acts as an active dressing. Corneosticker DS is the stratum corneum of the stratum corneum, the corneocyte of the corneocyte. Besides the anatomical dressing action Corneosticker DS is also able to reinforce the physiological barrier of the skin. From the surface of the skin, CORNEOSTICKER DS acts as a physiological dressing by reinforcing the buffering properties of the stratum corneum. It also provides an immediate humectant effect that contributes to reducing the Trans Epidermal Water Losses within 4 hours following an alteration of the stratum corneum.

2 % variation versus T % variation versus T % variation versus T IN VIVO TEST: ANALYSIS OF SKIN SURFACE DEPRESSIONS 2 Improvement of skin grain When CORNEOSTICKER DS is applied to the surface of the skin, it instantly fills in the cutaneous relief: -34% roughness on average. Number of cutaneous depressions after 2hours: - 6% and up to 32% Size of cutaneous depressions after 2hours: -% and up to 32% 1 1 Corneosticker T ImmediatelyA fter 2h After 8h Skin grain is instantly refined Immediately: +19% on average and up to +33% After 2H: +1% on average and up to +33% After 8H: +6% on average and up to +2% T2H Corneosticker DS improves the surface of the skin mmediately and till 8 hours after application with a better efficacy than the placebo. This demonstrates the benefits of the anatomical dressing action provided by Corneosticker DS. IN VIVO TEST: ANALYSIS OF SKIN GRAIN AND SOFTNESS Instant blurring action Corneosticker DS improves the surface of the skin mmediately and till 8 hours after application with a better efficacy than the placebo. This demonstrates the benefits of the anatomical dressing action provided by Corneosticker DS. IN VIVO TEST: ANALYSIS OF SKIN GRAIN AND SOFTNESS When CORNEOSTICKER DS is applied to the surface of the skin, it instantly fills in the cutaneous relief: -34% roughness on average Improvement of skin softness Corneosticker The biomaterial of Corneosticker DS displays the physical properties of a blurring agent. By providing a significant blurring effect Corneosticker DS contributes to blurring and therefore to masking cutaneous imperfections immediately after application Corneosticker 1 ImmediatelyA fter 2hA fter 8h 1 Skin is instantly softer Immediately: +22% on average and up to +67% After 2H: +18% on average and up to +67% After 8H: +9% on average and up to +67% ImmediatelyA fter 2hA fter 8h

3 % variation versus T % variation versus T Blurring effect of Corneosticker DS: Immediately: +21% and up to +4% After 2H: +14% and up to +33% After 8H: +6%* and up to +33% Example 2 before treatment Corneosticker 1 ImmediatelyA fter 2hA fter 8h Imperfections masked with Corneosticker DS: Immediately: +13% and up to +33% After 2H: +8% and up to +33% After 8H: no more visible By providing a significant blurring effect Corneosticker DS contributes to blurring and therefore to masking cutaneous imperfections immediately after application. After 2 weeks treatment This demonstrates that this restructuring action is not the result of the immediate film forming action of Cornesticker DS, but the daily improvement of skin depth thanks to the biomolecules composing the corneosphere recreated through CORNEOSTICKER DS. IN VIVO TEST: GLOBAL PERFECTING EFFECT AFTER 14 DAYS CORNEOSTICKER DS acts from the surface of the epidermis to improve its quality in depth. Repeated application for 2 weeks visibly and significantly improves the quality of the skin. 3 IN VIVO TEST: 2 WEEKS RESTRUCTURING ACTION The ageing mechanism leads to a change in the organization of cutaneous lines which change from an isotropic uniform state (lines oriented in all directions) in a young person, to a state where only deep furrows remain which lead to the formation of wrinkles (preferential direction). An increase in the percentage of isotropy characterizes a restructuring / anti-aging effect and therefore the smoothing effectiveness of the product Perfecting action +1%*** +12%*** +1%** +3%*** after 2 weeks treatment CORNEOSTICKER DS increases skin isotropy by +7% on average and up to +74% Example 1 before treatment Complexion Luminosity Skin Softness More luminous complexion Softer skin Finer skin grain Imperfections reduced Grain Finess Reduction in Imperfections Corneosticker DS acts from the surface of the epidermis to improve its quality in depth. HYDRASALINOL 3 SOLUTIONS IN 1 MOISTURIZING RESTRUCTURING SMOOTHING OUT After 2 weeks treatment HYDRASALINOL AND AQP8 TRANSPORT UREA, WHICH IS AT THE HEART OF HYDRATION AQP8, demonstrated for the first time in the human epidermis by the Codif International, opens up new opportunities for skin moisturizing

4 expression (% versus placebo) Particularly exposed to environmental aggressions such as solar radiation, wind, or pollution, our skin dehydrates, looses its radiance, firmness and becomes rougher and uncomfortable % We already know about aquaporin AQP3, which plays an important role in the transport of water. AQP8, produced by the keratinocytes of the epidermis, is an ammonium ion transporter, an essential precursor of urea synthesis. CODIF International s discovery places AQP8 at the center of urea metabolism, and revolutionizes the concept of cutaneous moisturizing. DISCOVERY OF AQP8 IN THE SKIN AND DEMONSTRATION OF AQP3 AQP8 and AQP3 were demonstrated on human skin and reconstructed epidermal tissues. Whilst AQP3 is expressed in the cell membranes, AQP8 was found in the cytoplasms of the suprabasal cells and the granular layer. 1 AQP8 +46% AQP3 Stimulates AQP8 (+198%) and AQP3 (+46%)synthesis in epidermis Increases by 43% mrna synthesis IN VITRO TEST: EFFECT OF HYDRASALINOL ON THE EXPRESSION OF BINDING PROTEINS Binding proteins are involved in inter-keratinocyte adhesions. A poor production of one of these proteins disrupts epidermal cohesion and therefore promotes water loss. The following are the most important of these proteins: desmocollin (DSC), desmoglein (DSG), and desmoplakin (DSP). 2 Hydrasalinol.% Hydrasalinol 1% Obtained by supercritical CO2 extraction, Hydrasalinol stimulates the expression of AQP8 in the epidermis, acting on all fronts against cutaneous dryness: production of urea, NMF, cellular cohesion, lipid matrix; this extract is an original and unique hydra-restructuring agent. Expression (% control) 1 1 stratum corneum DSCD SG DSP PKP1C3 DSC1 DSG1 IN VITRO TEST: EFFECT OF HYDRASALINOL ON THE PRODUCTION OF AQP8 AND AQP3 IN HUMAN EPIDERMIS stratum granulosum stratum spinosum Skin dryness is determined by external and internal factors. In both cases, it is essentially caused by a deficiency of Natural Moisturising Factors (NMF). PKP2 DSC3 DSG3 basal layer The major component of NMF is urea, produced by the mitochondria; it plays an essential role in skin hydration. It is therefore important to ensure its availability and its synthesis in the skin in order to maintain a high level of hydration. Immunolabeling of AQP8 Increases synthesis of binding proteins: Desmocollin (DSC): +13% Desmoglein (DSG): +228% Desmoplakin (DSP): +23% By increasing the synthesis of binding proteins, Hydrasalinol strengthens intercellular cohesion in the epidermis and limits water oss via hydric transfer. Hydrasalinol 1%

5 Expression (% control) (g/m2/h) Filaggrin Expression (% control) IN VITRO TEST: EFFECT OF HYDRASALINOL ON THE PRODUCTION OF FILAGGRIN The hydrolysis of filaggrin in the epidermis generates, amongst others, the release of 2 amino acids: histidine and glutamine, which are themselves the precursors of 2 fundamental elements of the NMF: urocanic acid and pyrrolidone carboxylic acid Hydrasalinol,% Hydrasalinol 1% Hydrasalinol increases the expression of Filaggrin by 9% Hydrasalinol increases the expression of these enzymes, which reflects stimulation of epidermal lipid metabolism, strengthening of the lipid barrier, improved epidermal impermeability, and therefore reduced water loss. CLINICAL TESTS: STUDY INTO THE HYDRA-RESTRUCTURING POWER OF HYDRASALINOL ON DRY SKIN Effect of Hydrasalinol 1% on skin hydration % compared with placebo Evaluation of the moisture level using Corneometry +4% +83% +7% 2h 4h 6h D +26% Hydrasalinol 1% Hydrasalinol, compared to placebo, increases moisture levels by a factor of 6. It acts as a dynamic and intelligent regulator for epidermal water content and compensates water losses in a regulated and proportional manner. D2 x6 D28 This is reflected by a reinforcement of the NMF, and therefore improved water retention in the epidermis. Trans-Epidermal Water Loss, Atmosphere IN VITRO TEST: EFFECT OF HYDRASALINOL ON THE METABOLISM OF EPIDERMAL LIPIDS -, D2 D28 Some of the numerous enzymes produced by the keratinocytes are involved in the synthesis of epidermal lipids, which form the intercellular cement. This cement is thought to be a major component of the epidermal barrier. Inhibition of Trans-Epidermal Water Loss -1-1, Corneal layer Several enzymes have a key role in the production of the lipids of the stratum corneum, which strengthens the epidermal barrier: Acetyl CoA Synthetase (AcCoS): synthesis of free fatty acids and cholesterol Serin Palmitoyl Transferase (SerPT) : ceramids synthesi Fatty Acid Synthase (FAS): fatty acids synthesis Ceramid Glucosyl Transferase (UGCG) : ceramids synthesis -2 Hydrasalinol CLINICAL TESTS: STUDY INTO THE HYDRA-RESTRUCTURING POWER OF HYDRASALINOL ON DRY SKIN 4 Hydrasalinol.2% Hydrasalinol.% 426 In untreated dry skin, the urea loss gradually increases while Corneometry and TEWL values do not Hydrasalinol 1% Thus, the measurement of the amount of extractable urea is independent on corneometry and TEWL. This therefore constitutes an original measure, allowing to the evaluation of a new parameter, different and complementary from hydration. AcCoS SerPT FASU GCG

6 TEUL variation (mg/dl) Corneometry index Urea loss (mg/dl) and TEWL (g/m 2 /h) DRY SKINS The discovery of AQP8 in the epidermis leads the CODIF Recherche et Nature laboratories to investigate a new means of moisturizing the skin. The development of Hydrasalinol has made it possible to rapidly assess the scope of this discovery. By activating the synthesis of AQP8 in the skin, Hydrasalinol acts at the heart of urea metabolism, to produce an immediate moisturizing action for even the driest skins. Its combined action on the binding proteins of the epidermis and lipid cement of the cornified layer increases the cohesion of the skin and reduces water losses for a visible and prolonged action. Urea Corneometry TEWL Introduction of a new concept: the Trans-Epidermal Urea Loss (TEUL) equivalent to the Trans-Epidermal Water Loss (TEWL) for water. CLINICAL TEST: EFFECT OF HYDRASALINOL ON TEUL, 1,2,9,6,3 -,3 -,6 -,9 untreated control placebo emulsion Emulsion with Hydrasalinol.2%,86,61 D1-D -,8 1,38,1 D28-D -,8 DERMOCHLORELLA Skin restructuring From the age of 2, our cells start to produce less collagen, elastin, sebum and then the skin dries out, becomes thinner and loses its elasticity. Wrinkles and stretch marks are the result of this lack of skin elasticity. Stretch marks appear when the elastic fibres of the dermis tear. Frequently they are located on the thighs, hips, breasts and buttocks due to a rapid weight gain or loss, pregnancy, puberty... Dermochlorella is an extract of a green microalgae Chlorella vulgaris, rich in peptides and amino acids, acts on all these elements of the dermal structure. The space surrounding the cells contains macromolecules, polysaccharides or glycosaminoglycans, fibrous protein, salts and water which as a whole are designated as the extracellular matrix, responsible for tissue cohesion. The main structure proteins are collagen and elastin. The extracellular matrix components are synthesized and secreted by cells such as the fibroblasts and degraded by enzymes called MMP (Matrix MetalloProteinase) whose activity is inhibited by endogenous antagonists called TIMP (Tissue Inhibitor of Metalloproteinase). By increasing the synthesis of AQP8 in epidermis, Hydrasalinol, from.2%: totally inhibits the Trans-Epidermal Urea Loss within 24 hours increases urea content in epidermis, by promoting transport and production IN VITRO TEST: EFFECT ON COLLAGENS 1 AND 3 Collagen is the main fibre protein of the body which gives tissues their elasticity. Its role may be compared to that of a frame. It is composed of different types depending on their location and it is essential for the healing process. REVEAL: HYDRA-RESTRUCTURING EFFECT OF HYDRASALINOL ON DRY SKIN 6 Control Dermochlorella D 1% Hydrasalinol boosts skin hydration for a redensifying, and hydra-restructuring effect. The roughness, characteristic of dry skins, disappears in favor of a suppler and smoother skin. Gene expression (%) % +1% COL 1 COL 3 D D28 Dermochlorella increases collagen in fibroblasts: Collagen I by +333% Collagen III by +1% Hydrasalinol.2%

7 Gene expression (%) IN VITRO TEST: EFFECT ON ELASTIN AND ELAFIN Elastin is a glycoprotein secreted by dermis cells which has elastic properties. Its synthesis decreases with age resulting in the appearance of stretch marks under the action of mechanical constraints. Elafin is a specific inhibitor of elastase, an enzyme responsible for elastin fibre degradation. Gene expression (%) Control Dermochlorella D 1% Elastin +3% Dermochlorella increases: Elastin by +3% in fibroblasts Elafin by +183 in keratinocytes Elastin +183% several types of laminins. They represent the major non-collagenic components. The isomers present are laminin and 6. They have a major structural role with the formation of a network to which other collagenic or noncollagenic proteins bind The degradation of the DEJ results in a reduction in the exchange surface between the epidermis and the dermis which can even result in the detachment of the epidermis with rubbing. IN VITRO TEST: EFFECT ON THE EXPRESSION OF PROTEINS PRESENT IN THE DEJ Gene expression (%) % Control Dermochlorella D 1% +41% +37% +6% COL 4 LAM 6 LAM C OL 7 IN VITRO TEST: EFFECTS ON TIMPS EXPRESSION TIMPs are capable of inhibiting all MMPs. Therefore, they play a key role in maintaining a balance between extracellular matrix formation and degradation in various physiological processes % Control Dermochlorella D 1% 2% 31% TIMP 1 TIMP 2 TIMP 3 Dermochlorella increases TIMPs in dermal cells: TIMP-1: +% TIMP-2: +2% TIMP-3: +31% In fibroblasts Dermochlorella increases: Collagen IV by +77% Laminin 6 by +41% In keratinocytes Dermochlorella increases: Laminin by +37% Collagen VII by +6% CLINICAL TEST: EFFECT ON SKIN FIRMNESS AND TONE * -.2 Cutaneous penetration Absorption Amplitude THE DERMIS-EPIDERMIS JUNCTION: ATTACHMENT POINT BETWEEN THE EPIDERMIS AND THE DERMIS The skin contains the Dermis-Epidermis Junction (DEJ) or basal membrane which ensures an optimum cohesion between the dermis and the epidermis. Initially it is sinusoid in shape, and becomes flatter with age: the dermis is less well attached to the epidermis. It contains specific molecular components: collagen glycoproteins, the main components in the extracellular matrix: type IV collagen provides the mechanical stability of the basal membrane and type VII collagen is the major component of anchoring fibrils * : p <.1 Treated with Dermochlorella 1% Untreated control Results after 84 days of use: Cutaneous penetration: -7.4% and up to -26% A decrease in this parameter indicates that the bead creates only a slight depression on the skin => the skin is firmer Absorption of bounces by skin: +6.% and up to +66% An increase in this parameter indicates that the bounces stop sooner => the skin tone increased Amplitude of bounce: -1.% and up to -46% A decrease in this parameter indicates that the bead bounces less intensely => the firmness and tone of the skin increased.

8 Number of skin lesions ANTI-ACNE ACTIVE SYSTEM Amazon rainforest oil complex Anti-Acne Active System is oil complex derived from Amazon rainforest plants: Andiroba, Copaíba and Açaí. It contains actives such as Flavonoids, Beta-caryophyllene and Limonoids % -12% % -42% D-D -21D -42D -6 In the period of 6 days treatment with Anti-Acne System, skin lesions are reduced by 42% References: 1. Codif International products technical files 2. Beraca product catalogue