I hope that you will find our product range useful for your professional activity.

AKNICARE NEW FORMULA LET S FOCUS ON ACNE A COMPLETE AND INNOVATIVE RANGE OF MEDICAL DEVICES TO CONTROL MILD-MODERATE COMEDONIC AND INFLAMMATORY ACNE

Dear Doctor, I would like to take a few moments of your time to introduce you to the range of products produced by our company. The products are Class IIa and Class III medical devices certified by Istituto Superiore di Sanità (the scientific body of the Italian National Health Service) designed for the purpose of controlling, reducing and treating mild-moderate comedonic and inflammatory acne. These products work by controlling the microenvironment of the pilo-sebaceous unit. The changes generated by the combination of Triethyl Citrate and Ethyl Linoleate (General Topics patent) at the level of the pilo-sebaceous unit mainly aim at the qualitative and quantitative control of the sebaceous lipids. The consequences are that the sebum production decreases, the hyperkeratinisation of the pilo-sebaceous duct is prevented and impeded, and bacterial colonisation is inhibited. We have discovered that GT peptide-10, a peptide with an antimicrobial action which efficiently protects microbiologically the products, synergises very well with Triethyl Citrate to control bacterial colonisation. As a consequence of this logical and multifunctional approach, the medical devices are effective both for mild-moderate comedonal and inflammatory acne. is a systematic and complete range of products structured in such a way to offer you a wide range of therapeutic choices which includes: Products dedicated to cleanse acneic skin; Specific treatment products; Treatment products for make up, «care up»; Treatment products for sun protection. We have also developed innovative technologies such as the LIPIFREE Technology, which increases the products efficacy and whose sensorial characteristics increase the patient s compliance. I hope that you will find our product range useful for your professional activity. Best regards, Dr. Gianfranco de Paoli Ambrosi President

3 AN INNOVATIVE AND FOCUSED MECHANISM OF ACTION MULTIPHASE ACTION FOR CONTROLLING THE PILO-SEBACEOUS UNIT MICROENVIRONMENT ETHYL LINOLEATE direct action 5 α-reductase indirect action TRIETHYL CITRATE SEBORRHOEA TRIETHYL CITRATE -COOH TRIETHYL CITRATE + GT peptide-10 ETHYL LINOLEATE PPAR-γ ACTIVATION HYPER KERATINISATION BACTERIAL COLONIZATION GRAM+, GRAM- INFLAMMATION ETHYL LINOLEATE SCAVENGER OF ROS TRIETHYL CITRATE SEBACEOUS TRIGLYCERIDES HYDROLYSIS MILD-MODERATE COMEDONIC AND INFLAMMATORY ACNE Medical Devices perform a synchronised and multiphase action to control the pilo-sebaceous unit microenvironment. They act simultaneously on the three phases of acne etiopathogenesis which lead to inflammation: seborrhoea, hyperkeratinisation and bacterial colonisation.

4 CLINICAL EFFICACY DEMONSTRATED IN VITRO TRIETHYL CITRATE ACTIVATION BY BACTERIAL LIPASES HYDROLYSIS OF TRIETHYL CITRATE INDUCED BY BACTERIAL LIPASES Bacterial lipases hydrolyse Triethyl Citrate with a consequent release of carboxyl groups and a decrease in ph values at the pilosebaceous unit level. Data on file General Topics: University of Catania - Department of Pharmaceutical Sciences ph 7 6 5 4 3 2 1 6% 5,3% 5% 4,8% 4,5% 4% 3,8% 3,8% 0 0,5 1 1,5 2 4 5 6 Time (hours) (Graph 1) PROTECTION FROM THE HYDROLYSIS OF SEBACEOUS TRIGLYCERIDES PROTECTION OF SEBACEOUS TRIGLYCERIDES FROM HYDROLYSIS INDUCED BY BACTERIAL LIPASES DUE TO TRIETHYL CITRATE 100% 82% Triethyl Citrate is a preferential substrate for bacterial lipases in comparison with triglycerides. The in vitro data displayed here have also been confirmed by in vivo experiments (data not published). Data on file General Topics: ABICH 50% 18% 11% 17% 13% 0,5% 1% 5% 15 min 30 min 45% (Graph 2) CONTROL OF BACTERIAL COLONISATION INHIBITION OF BACTERIAL COLONISATION INDUCED BY TRIETHYL CITRATE Triethyl Citrate, once hydrolysed in situ by the bacterial lipases, causes a change in the pilo-sebaceous unit microenvironment that rapidly inhibits bacterial growth (assessment carried out on propionibacterium acnes). Data on file General Topics: Eurochem Log(10) [PBA] 7 6 5 4 3 2 1 t 0 t 2 t 4 t 24 t 48 t 168 Time (hours) Linear regression (Graph 3) GT PEPTIDE-10 AND TRIETHYL CITRATE The association between GT peptide-10 and Triethyl Citrate has shown a marked antimicrobial effect when faced with various bacterial families. Data on file General Topics: Microna Before After (Figure 1)

5 CLINICAL EFFICACY DEMONSTRATED IN VIVO CONTROLLING SEBORRHOEA JOURNAL COMPILATION 2007 BRITISH ASSOCIATION OF DERMATOLOGISTS BRITISH JOURNAL OF DERMATOLOGY 2007 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF A LOTION CONTAINING TRIETHYL CITRATE AND ETHYL LINOLEATE IN THE TREATMENT OF ACNE VULGARIS A. Charakida, M. Charakida and A.C. Chu - Department of Dermatology, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K. 150% 100% 108% 86% 92% 50% 43% PLACEBO t 0 t 12 weeks (Graph 4) The most remarkable result of this study is the evidence that the combination of Triethyl Citrate and Ethyl Linoleate reduces the production of sebum in treated patients in a clinically significant way. In a previous study, the erythromycin-zinc complex (for topical use) demonstrated a 20 % reduction in sebum production. This new lotion has demonstrated that it is more efficient in suppressing sebum secretion, reducing sebum production by an average of 53% after 12 weeks of treatment. SEBORRHOEA HYPERKERATINISATION BACTERIAL COLONISATION INFLAMMATION ON THE BASIS OF THE RESEARCH CARRIED OUT IT WAS DEMONSTRATED THAT, BY CHANGING AND CONTROLLING THE PILO-SEBACEOUS UNIT MICROENVIRONMENT, THE MEDICAL DEVICES ACT RAPIDLY AND EFFICIENTLY AGAINST BOTH COMEDONAL AND INFLAMMATORY LESIONS, WHICH LEADS TO PRESUME A SPECIFIC ACTION ON THE MAIN ETIOPATHOGENIC FACTORS OF ACNE.

6 TREATMENT - FACE cream (LIPIFREE Technology) Specific emulsion to control and diminish the signs of acne. It has a hydrating action which prevents dry skin and has a positive mattifying effect. Use: apply twice a day, unless otherwise prescribed by your doctor. Ingredients: Triethyl Citrate, Ethyl Linoleate, Salicylic Acid (0.5%), Zinc Lactate, Hyaluronic Acid, GT peptide-10. treatment lotion (Drysyst Technology) Alcoholic lotion specifically recommended to control and reduce acne symptoms in cases where a rapid and marked action is needed. The lotion is contained in a bottle with an auto-sterilizing applicator. Use: apply twice a day, unless otherwise prescribed by your doctor. Ingredients: Triethyl Citrate, Ethyl Linoleate, Salicylic Acid (0.5%), GT peptide-10. skin roller (Drysyst Technology) Alcoholic solution specifically formulated to combat the formation of isolated and contained acneic lesions and to favour their rapid disappearance. Use: apply using the special roller up to 8 times per day. Only apply on the isolated lesion. Ingredients: Triethyl Citrate, Ethyl Linoleate, Salicylic Acid (0.5%), GT peptide-10.

7 CLINICAL ASSESSMENT - FACE 10 ACNE SEVERITY (LEEDS REVISED GRADE) 50 48 COMEDONIC LESIONS 8 6 4 2 4 6 4 2 40 30 20 10 27 31 14 PLACEBO PLACEBO t 0 t 12 weeks t 0 t 12 weeks (Graph 5) THE SEVERITY OF THE ACNEIC SCENE WAS REDUCED BY AN AVERAGE OF 50% AFTER 12 WEEKS OF TREATMENT (Graph 6) THE NUMBER OF COMEDONIC LESIONS WAS REDUCED BY AN AVERAGE OF 55% AFTER 12 WEEKS OF TREATMENT 50 40 30 20 10 INFLAMMATORY LESIONS (PAPULES AND PUSTULES) 31 20 18 7 100 80 60 40 20 TOTAL LESIONS (COMEDONES, PAPULES AND PUSTULES) 86 52 49 21 PLACEBO PLACEBO t 0 t 12 weeks t 0 t 12 weeks (Graph 7) THE NUMBER OF INFLAMMATORY LESIONS WAS REDUCED BY AN AVERAGE OF 63% AFTER 12 WEEKS OF TREATMENT (Graph 8) THE TOTAL NUMBER OF LESIONS (COMEDONES, PAPULES AND PUSTULES) WAS REDUCED BY AN AVERAGE OF 57% AFTER 12 WEEKS OF TREATMENT BEFORE Photographic documentation T 0 AFTER Photographic documentation after 12 weeks of treatment (Photo 1)

8 TREATMENT - CHEST AND BACK CB chest & back (LIPIFREE Technology) Oil-free fluid emulsion spray characterised by an excellent tolerability and safety profile. It has been created to control and reduce the symptoms of comedonic and inflammatory acne of light to moderate severity on the chest and back. Use: apply twice a day, unless otherwise prescribed by your doctor. Ingredients: Triethyl Citrate, Ethyl Linoleate, Salicylic Acid (0.5%), GT peptide-10, Zinc Lactate, Hyaluronic Acid. spraying area 200 cm 2 APPLICATION It is recommended to spray the emulsion while keeping the nozzle at a distance of around 20 cm from the skin surface. Every spray releases around 0.2 ml, which is enough to cover an area of around 200 cm 2, for a total of 250 sprays. distance 20 cm LIPIFREE TECHNOLOGY LIPIFREE Technology allows for more effective results and at the same time makes the formulation of the product more pleasant, thus improving the patient s compliance. In the products, LIPIFREE Technology uses Triethyl Citrate as a functional carrier. The other liposolubles (Ethyl Linoleate, Salicylic Acid) are contained in the matrix made up of Triethyl Citrate and the micelles are stabilized by a special emulsifier characterised by an excellent safety profile. The other water-solubles are dissolved in the external phase of the emulsion. STANDARD O/W EMULSION In a O/W emulsion the internal oil phase is made up of lipids. The drops of these lipids are spread in the external aqueous phase. Oil phase in O/W standard emulsion LIPIFREE EMULSION In a O/W LIPIFREE emulsion, the main active ingredient, triethyl citrate becomes a functional carrier for the other liposolubes. Other main lipophilic active ingredients Trietilcitrato: active lipophilic ingredient Carrier in the LIPIFREE emulsion GT peptide-10 (Figure 2)

9 CLINICAL ASSESSMENT - CHEST AND BACK REDUCTION OF COMEDONIC AND INFLAMMATORY LESIONS Open study to evaluate the effectiveness and the tolerability of CB chest & back on 12 patients aged from 13 to 20 years, affected by light to moderate acne on the back and/or chest. Application of the emulsion for 12 weeks. Checks carried out at 4, 8, 12 weeks. Data on file General Topics: San Gallicano Institute, Prof. Enzo Berardesca - Rome 45 35 25 15 5 Inflammatory lesions TOTAL LESIONS COUNT Basal Week 4 Week 8 Week 12 Comedonic lesions (Graph 9) BEFORE Photographic documentation T 0 AFTER Photographic documentation after 12 weeks of treatment BEFORE Photographic documentation T 0 AFTER Photographic documentation after 12 weeks of treatment (Photo 2)

10 TREATMENT - SUN PROTECTION & CARE UP sun SPF 30 A fine and light emulsion with solar filters that reduce the effect of ultraviolet radiation for both UVB (SPF 30) and UVA rays (high protection). It has been specifically developed for acneic and seborrhoeic skin. Use: unless otherwise prescribed, after cleansing the skin apply at least two-three times per day, gently massaging until completely absorbed; reapply more frequently during sun exposure, for example after swimming or bathing. Ingredients: Triethyl Citrate, Hyaluronic Acid, GT peptide-10, solar filters. sun teintée SPF 30 Coloured emulsion with solar filters that reduce the effect of ultraviolet radiation, for both UVB (SPF 30) and UVA rays (high protection). It has been developed specifically for acneic and seborrhoeic skin. Use: unless otherwise prescribed, apply at least two-three times per day, gently massaging into the skin until a uniform colour is achieved; reapply more frequently during sun exposure, for example after swimming or bathing. Ingredients: Triethyl Citrate, Hyaluronic Acid, GT peptide-10, solar filters. cream teintée Coloured multifunctional emulsion developed to conceal and correct imperfections typical of impure skin, controlling and reducing at the same time the symptoms of acne. Available in two elegant colours: clair and doré. Use: after cleansing the skin, apply the product, unless otherwise prescribed by your doctor, two to three times per day by massaging gently until you get an even colouring. Ingredients: Triethyl Citrate, Ethyl Linoleate, Salicylic Acid (0.2%), Zinc Lactate, Hyaluronic Acid, GT peptide-10.

11 CLEANSING cleanser Monophasic solution with antiseptic and purifying action. It has a light exfoliating action for the daily cleansing of acneic and seborrhoeic skin. It has a positive effect on hyperkeratinisation as it frees the patient from excess greasiness and reduces epidermal thickness. To be used for cleansing face, shoulders, chest and back. Use: use like a liquid soap; apply on the skin by massaging gently, leave it on to act for about half a minute and then rinse it off well with water. Ingredients: Triethyl Citrate, Pyruvic Acid, Triclosan. gentle cleansing gel This gel corrects the typical imperfections of sensitive acneic and seborrhoeic skin, which is prone to reddening and getting dehydrated by concomitant treatments. It also has a soothing and antibacterial action. Use: apply the product on the skin and massage gently; it can be removed by rinsing with water or by using a cotton pad. Ingredients: Triethyl Citrate, MSM, GT peptide-10. MOTIVATIONAL RESEARCH CLEANSING IN PATIENTS WITH ACNE 100% 70% 50% 20% Very useful Useful Useless No response Do you believe that the prescription of specific cleansers is important when treating patients with acne? FROM THE RESULTS OF THE MOTIVATIONAL RESEARCH CARRIED OUT BY GENERAL TOPICS, IT HAS EMERGED THAT DERMATOLOGISTS CONSIDER THAT CLEANSING FOR PATIENTS WITH ACNE IS A FUNDAMENTAL TOOL (VERY USEFUL/USEFUL > 90%) TO INCREASE THE PATIENT S COMPLIANCE TO EVERY SUBSEQUENT TREATMENT. Data on file General Topics 10% 0% (Graph10)

AKNICARE A COMPLETE AND INNOVATIVE RANGE OF MEDICAL DEVICES TO CONTROL MILD-MODERATE COMEDONIC AND INFLAMMATORY ACNE GENERAL WARNINGS cream, treatment lotion, SR skin roller and CB chest & back Medical Devices contain 0.5% Salicylic Acid. cream teintée Medical Device contain 0.2% Salicylic Acid. Do not use these Medical Devices in the case of intolerance to Salicylic Acid or its derivatives. Do not use for individuals affected by salicylism. Do not use the products if the patient is being treated with anticoagulant medication. Do not use the products if you are allergic to any of the ingredients. Unless otherwise prescribed by your doctor, do not use the products for children younger than 12 years of age or during pregnancy or breastfeeding. USEFUL INFORMATION The product treatment lotion is a Medical Device containing Ethylic Alcohol and it may dry some individuals skin; as an alternative use the Medical Device cream. Always bear in mind that even though Salicylic Acid is present in relatively low concentrations (0.5%), CB chest & back is destined to be applied onto large areas of skin. Inform the patient that the application of sun and sun teintée must be repeated after bathing, showering or any sporting activity. 0373 S CT DW U O RL ID E H E A LT H C A R E P RO D THE FUTURE IS OPEN y pan General Topics s.r.l. Località Santigaro, 32-25010 San Felice del Benaco (BS) - ITALY - Tel. +39 0365 522617 - Fax +39 0365 522619 www.general-topics.com +E - Rev. 1-2013 Copyright GENERAL TOPICS s.r.l. All rights reserved GE CS RAL TOP I NE Com W +E-SFI-UK-2 Assessment of CE marking performed by the Italian accredited body I.I.S.