EN_SA Fillers-Training-B2B Fill&Care-2408.pptx

Toskanimed filler b2b presentation

1. SKIN ARCHITECT FILL&CARE TOSKANIMED – Training for distributors

2. Aesthetic Medicine PAST Focus on volume and wrinkle correction PRESENT Priority on safety and natural results FUTURE FILL&CARE : regeneration and restoration TOSKANIMED – Training for distributors

3. FILL&CARE REGENERATION Promotes the regeneration of fatty tissue RESTORATION Increases structural proteins of the skin FILL Comprehensive approach to skin health TOSKANIMED – Training for distributors

4. ONLY HYALURONIC ACID TOSKANIMED – Training for distributors

5. STANDARDIZED PROCESS Sterile manufacturing process from start to finish Hyaluronic acid 3000 kDa Low degree of cross-linking Molecular integrity Monophasic hyaluronic acid Homogeneous hyaluronic acid CROSS-3000 Technology TOSKANIMED – Training for distributors

6. 3.000 kDa Double duration Biostimulates structural cells High biocompatibility LOW LEVEL OF CROSS-LINKING Structural integrity Low levels of BDDE Health friendly High Molecular Weight TOSKANIMED – Training for distributors

7. COHESIVE Integral structure Resistant to breakage MONOPHASIC Only cross-linked HA Filler effect HOMOGENEOUS Same molecular weight Therapeutic effect Optimal structure TOSKANIMED – Training for distributors

8. FILL &CARE TOSKANIMED – Training for distributors

9. Improved Durability HIGH MOLECULAR WEIGHT Longer absorption time LESS CROSS-LINKING Fewer access points for hyaluronidases HYALURONIDASE-2 Less active in high weight HA 1 2 3 TOSKANIMED – Training for distributors

10. Rheological Parameters G’ > G’’ GREATER RIGIDITY ( more elastic than viscous ) GREATER RIGIDITY ( more viscous than elastic ) Minimum deformation Moderate deformation G’ < G’’ G’ (Elastic Modulus) Ability to recover its initial shape G’’ (Viscous Modulus) Inability to recover its initial shape Tan δ ( Tangential Delta) (G’ / G’’) determines the stiffness of the filler TOSKANIMED – Training for distributors

11. Tan δ / Tangential Delta Viscous / Liquid Elastic /Gel SUBLIME DENSITY VOLUME HA concentration 20 mg/ml 23 mg/ml 26 mg/ml Degree of cross-linking < 0,01 ppm < 0,01 ppm < 0,01 ppm G’ / Elastic modulus 140 Pa 270 Pa 425 Pa TOSKANIMED – Training for distributors

12. Filling Effect I: Filler SUBLIME Greater fluidity, perfect integration and ideal for fine structures and fine wrinkles DENSITY Versatile and with greater elasticity, ideal for correcting wrinkles and expression lines VOLUME High elasticity, ideal for mobile structures and for volumization or modeling TOSKANIMED – Training for distributors

13. Filling Effect II: Biostimulation of Fibroblasts FIBROBLASTS Improves the physiology and rejuvenates STRUCTURAL PROTEINS Increased generation of collagen and elastin EXTRACELLULAR MATRIX Restoration of the natural structure TOSKANIMED – Training for distributors

14. Filling Effect II: Biostimulation of Adipocytes HYPODERMIS Deeper layer with fat cells STEM CELLS Generation and maturation of adipocytes NATURAL VOLUME Natural volumization and restructuring Stem cell derived from adipose tissue Pre-adipocyte Mature adipocyte TOSKANIMED – Training for distributors

15. FILL& CARE TOSKANIMED – Training for distributors

16. Biocompatibility 1 Similarity Mimics the skin's natural hyaluronic acid 2 Integration Perfect acceptance in skin tissues 3 Prevention Avoid adverse reactions of the immune system TOSKANIMED – Training for distributors

17. Benefits Insured Volume Restoration of facial structure Correction Visible reduction of wrinkles Hydration Supply of skin hydration Glow Improves the appearance of the skin TOSKANIMED – Training for distributors

18. High Security Profile CE class III Medical device ISO 13485 Quality compliance GMP Sanitary requirements Bacterial Endotoxins Skin Architect Filler ≤ 0,5 UE/ml EU Regulation < 20 EU/ml Residual levels of BDDE Skin Architect Filler < 0,1 ppm EU Pharmacopoeia / FDA < 2 ppm TOSKANIMED – Training for distributors

19. Focus on the Patient 1 TRUST In the doctor and the brand 2 SATISFACTION Natural results 3 AESTHETIC FOOTPRINT Long- term security TOSKANIMED – Training for distributors

20. TREATMENT TOSKANIMED – Training for distributors

21. TOSKANIMED – Training for distributors

22. TOSKANIMED – Training for distributors

23. Results Courtesy Dra. Carolina Correoso (Madrid) Treatment Gummy smile + lip volume Product 0,5 ml Skin Architect Sublime TOSKANIMED – Training for distributors Before Immediately after Before Immediately after

24. Courtesy Dra. Patxi Rubio (Barcelona) Treatment Facial harmonization Product 1,5 ml Skin Architect Volume 0,5 ml Skin Architect Density Results TOSKANIMED – Training for distributors Before Immediately after

25. Courtesy Dr. Richard Rocha (Madrid) Treatment 1 ( lower third ) Chin protection Product 2 ml Skin Architect Volume Treatment 2 Definition of mandibular angle Product 2 ml Skin Architect Volume Treatment 3 Definition of the mandibular line Product 1 ml Skin Architect Volume Results TOSKANIMED – Training for distributors

26. Courtesy Dra. Laura Cotter (Madrid) Treatment 1 ( middle third ) Mesosynergy Product Peeling Radiance + NCPR & WCPR + HA3 2 ml Skin Architect Volume 1 ml Skin Architect Density Treatment 2 ( lower third ) Definition of mandibular line Product 1 ml Skin Architect Volume Results TOSKANIMED – Training for distributors

27. Results Courtesy Dr. Richard Rocha (Madrid) Treatment 1 ( middle third ) Product 2 ml Skin Architect Volume Treatment 2 ( middle third ) Nasolabial fold Product 1 ml Skin Architect Sublime TOSKANIMED – Training for distributors

28. BENCHMARK TOSKANIMED – Training for distributors

29. Brand Product [HA] (mg/ml) Cross- linking technology Degree of cross-linking (%) G’ / Elastic modulus ( Pa ) Revolax Fine 24 Ursolic acid encapsulated Unknown 167 Sub-Q 24 Ursolic acid encapsulated Unknown 246 Deep 24 Ursolic acid encapsulated Unknown 344 Texoane Redensity II 15 Standard Unknown 80 RHA 1 15 RHA 1,9% Unknown RHA 2 23 RHA 3,6% Unknown RHA 3 23 RHA 6,02% 261 RHA 4 23 RHA 6,85% 346 Ultra-Deep 25 Standard 10% 366 Juvederm Vobella 15 Vycross 6,61% 239 Volift 17.5 Vycross 7,73% 350 Voluma 20 Vycross 7,36% 493 Volux 25 Vycross 9,4% 677 Restylane Fynesse 20 OBT 0,1%-5% Unknown Volyme 20 OBT 0,1%-5% Unknown Refyne 20 OBT 6% Unknown Defyne 20 OBT 8% Unknown ToskaniMed Sublime 20 CROSS-3000 1,67% 140 Density 23 CROSS-3000 1,71% 270 Volume 26 CROSS-3000 2,22% 425 TOSKANIMED – Training for distributors

30. TOSKANIMED – Training for distributors BRAND % CROSS-LINKING TEOSYAL ULTRADEEP 10,00% JUVEDERM VOLUX 9,40% RESTYLANE DEFYNE 8,00% JUVEDERM VOLIFT 7,73% JUVEDERM VOLUMA 7,36% TEOSYAL RHA4 6,85% JUVEDERM VOLBELLA 6,61% TEOSYAL RHA3 6,02% RESTYLANE REFYNE 6,00% RESTYLANE VOLYME 0,1-5% TEOSYAL RHA2 3,60% SKIN ARCHITECT SUBLIME 2,22% TEOSYAL RHA1 1,90% SKIN ARCHITECT VOLUME 1,71% SKIN ARCHITECT DENSITY 1,67% MODELHA LIPS 1,50% MODELHA VOLUME 1,50%

31. TOSKANIMED – Training for distributors

32. CONCLUSIONS TOSKANIMED – Training for distributors

33. FILL CARE IMPROVED DURATION Unique features of 3,000 kDa hyaluronic acid OPTIMIZED RHEOLOGY Fillers adapted to the needs of each treatment and anatomical region DOUBLE FILLING EFFECT Volumization by hyaluronic acid and cellular biostimulation BIOCOMPATIBILITY The 3,000 kDa hyaluronic acid simulates the skin's own HA, avoiding rejection SECURITY PROFILE Provides confidence and protection to patients and doctors AESTHETIC FOOTPRINT Short and long-term benefits, offering natural results TOSKANIMED – Training for distributors

34. SKIN ARCHITECT INNOVATION New generation of dermal fillers EFFECTIVENESS Visible and long-lasting results SECURITY Highest standards of quality and purity SATISFACTION Benefits for doctors and patients

35. FAQs Approximately how long do Skin Architect Fillers last? This is a characteristic that depends on each patient: their metabolism, lifestyle, diet, genetics and, very importantly, the anatomical area (lasting up to two years in areas with little circulation and movement, such as the nose in rhinomodelling treatments). Likewise, the duration of our fillers depends on their HA concentration, with Sublime: 8-9 months, Density: 9-10 months and Volume: 11-12 months, and it also depends on the nature of the HA molecule, such as its degree of cross-linking and molecular weight. A highly cross-linked molecule has more points of union with hyaluronidases, while HA with a very high molecular weight is degraded by the least active type of hyaluronidase of all the hyaluronidase enzymes in the body. To this duration, we must add the biostimulating FILL effect of our FILL&CARE concept. The biostimulating action of our product activates skin rejuvenation, reactivating the cellular proliferation of adipose tissue in the hypodermis and increasing the fibroblast population, all of which provides volume naturally over time, even when the injected HA has already degraded. Furthermore, it should be noted that this duration is in an isolated treatment with Skin Architect fillers. If a comprehensive treatment such as Mesosynergy is performed, by preparing the skin by cleaning impurities and previously stimulating the regeneration and rejuvenation of the skin, any subsequent treatment will be more long-lasting and effective. TOSKANIMED – Training for distributors

36. What molecular weights do the competing products have and which one do we compare ourselves to for similarity? Currently, few laboratories have talked about molecular weight, but by reviewing the degrees of cross-linking, the molecular weight and its speed of degradation can be extrapolated. The more cross-linking, the more points of union with hyaluronidases (faster degradation) and even if high molecular weights are achieved, the HA molecules are less and less similar to those that the skin presents naturally (endogenous HA). Does the application of the product cause pain or stinging? Our fillers do not currently have lidocaine, although in certain patients and certain areas of application it makes the treatment more comfortable (areas such as lips). The reason for this is that lidocaine is a drug that recurrently causes allergies and, in addition, in our fillers the pain during application is low and very tolerable. In any case, a topical anesthetic can always be applied shortly before treatment. We also know that burning or stinging sensations are common with fillers on the market, but in our case this is not usually the case (as always, it depends on the patient). This is due to the rheology of Skin Architect fillers, especially the viscosity (G’’), which makes the product integrate and flow evenly between the skin tissues. But it should be noted that the greater the amount of product or concentration, the more space it will occupy between the tissues and the greater the sensation of discomfort it will generate. Can the application of Skin Architect Fillers be combined with other treatments and devices? Of course, we actively promote the Mesosynergy approach to purify the skin of impurities and nourish it with biostimulant substances from our laboratory to promote skin regeneration and rejuvenation. FAQs TOSKANIMED – Training for distributors

37. References Dr.Kroman . Fuerza de extrusión. An Open- Label Study of the Safety and Effectiveness of   Crosslinked Hyaluronic Acid 18mg/ml, Crosslinked Hyaluronic Acid 23mg/ml) and Crosslinked Hyaluronic Acid 26 mg/ml) Lab . Kroman . Kuo J-W. Practical aspects of Hyaluronan based medical products . Boston: Taylor and Frances. 2005: pp 1-209 Gavard Molliard S, Bon Bétemps J, Hadjab B, Topchian D, Micheels P, Salomon D. Key rheological properties of hyaluronic acid fillers: from tissue integration to product degradation . Plast Aesthet Res 2018;5:17. http:// dx.doi.org/10.20517/2347-9264.2018.10 Samuel J. Falcone, Richard A. Berg . Crosslinked Hyaluronic acid dermal fillers: a comparison of rheological properties . J. Biomed Material Research A. 2008 Oct; 87(1): 264-71 Stefano Santoro, Luisa Russo, Vincenzo Argenzio , Assunta Borzacchiello . Rheological properties of cross-linked hyaluronic acid dermal fillers. J Appl Biomater Biomech 2011, Vol.9, No.2, 127-136 Wongprasert P. at al, A critique of current characterization methods . Dermatologic therapy.2022 35 (6):e15453 Kruglikov IL, Wollina U. Soft tissue fillers as non- specific modulators of adipogenesis : change of the paradigm ? Exp Dermatol . 2015;24(12):912-5. Wollina U. Midfacial rejuvenation by hyaluronic acid fillers and subcutaneous adipose tissue —a new concept. Med Hypotheses . 2015;84(4):327-30. Nadra K, Andre M, Marchaud E, et al. A hyaluronic acid-based filler reduces lipolysis in human mature adipocytes and maintains adherence and lipid accumulation of long-term differentiated human preadipocytes . J Cosmet Dermatol . 2021;20(5):1474-82. Safa M, Natalizio A, Hee CK. A Prospective, Open- Label Study to Evaluate the Impact of VYC-12L Injection on Skin Quality Attributes in Healthy Volunteers . Clin Cosmet Investig Dermatol . 2022;15:411-26. Wongprasert P, Dreiss C, Murray G. 2022. “ Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods ”. Dermatological Therapy . DOI: 10.1111/dth.15453 TOSKANIMED – Training for distributors