Breakthrough Innovations from SkinMedica

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Breakthrough Innovations from SkinMedica Jeanine Downie, MD Director Image Dermatology, Montclair, NJ 1 SOLAR RADIATION IS MORE THAN JUST UV! 400 760 100 1x10 6 wavelength (nm) Most sunscreens only provide protection against UV exposure Adapted from: Dupont E, et al. Int J Cosmetic Sci. 2013;35:224-232 2 1

PRIMARY DAMAGE FROM SOLAR RADIATION Grether-Beck S, et al. Photodermatol Photoimmunol & Photomed. 2014;30:167-174 3 Do Therapeutic Uses of IR Cause Damage? Inflammatory Conditions Reduces proinflammatory cytokine/chemok ine production Muscle Enhances performance and decreases postexercise damage and inflammation NO! Key Difference is CONTROL!!! Intensity of Radiation Treatment Time Heat Generation Location Wound Healing Improves wound healing by up to 150% Recovery time between multiple treatments Akhalaya M. Ya, et al. Ageing Research Reviews. 2014;16:1-11de Almeida P, et al. Photochemistry and Photobiology. 2011;87(5):1159-1163. Hopkins JT, et al. Journal of Athletic Training. 2004;39(3):223-22. Yamaura M, et al. Lasers Surg Med. 2009;41(4):282-290. 4 2

TOTAL DEFENSE + REPAIR DEFENDS Helps prevent damage caused by IR-A, UVA, and UVB Helps fight free radicals Helps maintain the dermal matrix REJUVENATES Helps amplify the skin s ability to rejuvenate itself Helps correct signs of photodamage and photoaging It s not just a sunscreen. It s a multi-modal rejuvenating SUPERSCREEN. 5 Dunaliella salina Micro-algae from dead sea Polygonum aviculare Knotgrass extract rich in antioxidants UV UV IR-A SOL-IR Advanced Antioxidant Complex UV Secondary blend of antioxidants Tocopherol, green tea extract, melanin, niacinamide, ubiquinone, tocopheryl acetate and hydroxyacetophenone UV Heat Physalis angulata Wild gooseberry extract SPF actives Titanium dioxide &/or Zinc oxide Octinoxate, Octisalate 6 3

Total Defense Defense + Repair 7 Prevention of IR Damage: Study Design Tissue analysis 24h 4d D0 D1 D2 D3 D4 D5 D6 D7 D8 D9 Treatment with SOL-IR Advanced Antioxidant Complex Human skin explants stabilized IR-A radiation 720 J/cm 2 No SPF Actives! Time (days) Anti-MMP1 antibody detecting presence of MMP-1 protein Anti-tropoelastin antibody detecting the presence of elastin monomers - Natural IR-A exposure during summer in Munich: 75 J/cm 2 per hour (1) - IR-A 200 J/cm 2 triggers a 2.5-folds increase in MMP-1 (2.5 h exposure to solar radiation in the summer, southern Germany). - Increase in mitochondrial ROS production is detected after 30 J/cm 2 of IR-A radiation (2). (1) Schieke et al, Photodermatol Photoimmunol Photomed 19:228-34, 2003 (2) Schroeder et al, Free Radic Biol Med 43:128-35, 2007. 8 4

Lower MMP1 Staining with Sol-IR IR-A SOL-IR TM + IR-A 4 days after IR-A 24 h after IR-A Control Tissues were treated with 2 µl/cm2 of product from day 0-8. D5: IR-A radiation (720 J/cm2). Product was applied 3 h before IR-A radiation this day. 9 Greater Tropo-Elastin Staining Papillary Dermis IR-A SOL-IR TM + IR-A 4 days after IR-A 24 h after IR-A Control 10 5

Greater Tropo-Elastin Staining Upper Reticular Dermis Control IR-A SOL-IR TM + IR-A 4 days after IR-A 24 h after IR-A 11 Prevention of UV Damage: Study Design Treatment Tissue analysis D0 D1 Time 24 hours Reconstructed human skin UVB radiation 200 mj/cm 2 (~5 MED) 12 6

Sunburn Cells Control UVR TD+R SPF34 + UVR 24 Time of recovery (h) 16 6 13 Cyclobutane Pyrimidine Dimers (CPD) Control UVR (TD+R SPF34) + UVR 14 7

Total Defense Repair + Repair 15 Repair of UV Damage: Study Design Formulations Tissue analysis D0 D1 Time 24 hours Reconstructed human skin stabilized UVB radiation 200 mj/cm 2 (~5 MED) Sunburn followed by product application 16 8

DNA Repair Enzymes DNA Repair Enzymes repair damaged sections of DNA in a multi-step process inside the nucleus Topically applied DNA Repair Enzymes do not penetrate into the nucleus Kamileri I et al., Cell 2012 17 Stimulation of XPA1 with Sol-IR UVR Formulations Recovery 3 XPA1 * 2.5 Relative quantity (RQ) 2 1.5 1 0.5 0 Control UVR SPF34 TD+R SPF34 SOL-IR NO YES UVR 18 9

Stimulation of COL1A1 and COL3A1 with Sol-IR UVR Formulations Recovery 1.6 1.2 COL1A1 * 1.6 1.2 COL3A1 * Relative quantity (RQ) 0.8 0.8 0.4 0.4 0 Control UVR SPF34 TD+R SPF 34 0 Control UVR SPF34 TD+R SPF 34 SOL-IR NO YES SOL-IR NO YES UVR UVR 19 TOTAL DEFENSE + REPAIR Clinical study highlights 20 10

Subject 001-54yrs Subject 014-63yrs Week 12 Baseline 100µm Investigator: Dr. David McDaniel, The McDaniel Institute of Anti-Aging Research Mutant p53 staining 26 Significant improvements in key photodamage parameters over time Fitzpatrick Wrinkle Assessment 0-2 -4-6 -8-10 -12-14 -16-18 -20 n=24; Dr. David McDaniel, The McDaniel Institute of Anti-Aging Research Week 4 Week 8 Week 12 27 11

ARE ALL ANTIOXIDANTS CREATED EQUAL? Total Defense + Repair SPF 34 and SPF 50+ SKM antioxidant blend is a unique blend including state of the art technology. Vitamin C, E, Ferulic Acid Solution + SPF 30 Step 1: Low-pH L-Ascorbic acid. Stem 2: SPF 30 product SPF 50 with DNA repair enzyme & Antioxidants A new combination of classical antioxidants plus DNA repair enzymes. 28 PREVENTION OF UV DAMAGE Clinical design UVR (3 MED) Biopsy analysis D1 D2 D3 D4 D5 D6 D7 D8 D9 D10 24 hours Study subject volunteers were treated with formulations Formulation was applied 2h and wiped off before UVR. 29 12

Lower UV-Induced Erythema from Sol-IR 16 Untreated UV Control Mean erythema (a*) 12 8 4 Vit C+E+Ferulic Acid & SPF 30 (2 products) DNA Repair + AOX SPF 50 TD+R SPF 34 0 1 2 MED 3 Randomized, double-blind, single-center study (n=20) skin types II-III. Applied once daily for 10 days. On D10 product is applied 2h before UV-exposure. (lower a* = less erythema). Mean a* values for all test products were significantly lower than Untreated (all p=0.002). 30 Lower CPDs Staining in Human Biopsies Untreated/ non-irradiated TD+R SPF 34 Vit.C, E, Ferulic antioxidant + SPF 30 (2 products) Radiated, untreated TD+R SPF 50 DNA rep. enzymes, antioxidants, SPF 50 (1 product) 31 13

Lower CPDs in Human Biopsies with SOL-IR 5 4 4.6 Staining Scoring Criteria: 0 : No positive cells 1 : Very weak 2 : Weak 3 : Moderate 4 : Strong 5 : Very strong Score 3 2 1.7 2.9 1.8 2.2 1 0.2 0 Untreated, nonradiated Radiated, untreated TD+R SPF 34 Vit.C based AOX+SPF 30 (2 products) TD+R SPF 50 DNA repair AOX SPF 50 (1 product) Randomized, double-blind, single-center study (n=20) skin types II-III. Applied once daily for 10 days. On D10 product is applied 2h before and wiped off completely prior to UV-exposure. 32 Lower Mutant p53 Staining in Human Biopsies Untreated/ non-irradiated TD+R SPF 34 Vit.C based antioxidant + SPF 30 (2 products) Radiated, untreated TD+R SPF 50 DNA repair enzymes, antioxidant, SPF 50 (1 product) 33 14

Lower Mutant p53 in Human Biopsies 5 4 3.9 3.7 Staining Scoring Criteria: 0 : No positive cells 1 : Very few 2 : Few 3 : Some 4 : Several 5 : Many 3.7 Score 3 2.5 2.9 2 1 0.6 0 Untreated, nonradiated Radiated, untreated TD+R SPF 34 Vit.C based AOX+SPF 30 (2 products) TD+R SPF 50 DNA repair AOX SPF 50 (1 product) Randomized, double-blind, single-center study (n=20) skin types II-III. Applied once daily for 10 days. On D10 product is applied 2h before and wiped off completely prior to UV-exposure. 34 PA++++ SFP34 PA++++ SFP50+ PA++++ Highest UV-A Protection as measured by Japanese JCIA Standards (ISO 24442) of UV-A protection grade Protection Grade UVAPF (PPD) PA+ 2 to 4 PA++ 4 to 8 PA+++ 8 to 16 PA++++ more than 16 35 15

THANK YOU 36 IMPORTANT! SUNSCREEN IS REQUIRED TO OPTIMIZE AND MAINTAIN THE RESULTS OF USING THE LYTERA SKIN BRIGHTENING SYSTEM. CAUTION: Women should not use LYTERA or Retinol Complex if they are pregnant, lactating, or planning to become pregnant. Sunburn Alert: AHA/BHA Exfoliating Cleanser contains an alpha-hydroxy acid (AHA) that may increase the skin s sensitivity to the sun and particularly the possibility of sunburn. Patients should use a sunscreen, wear protective clothing, and limit sun exposure while using this product (or this system) and for a week following. Most of the SkinMedica products described here are intended to meet the FDA's definition of a cosmetic product, an article applied to the human body to cleanse, beautify, promote attractiveness, and alter appearances. These SkinMedica products are not intended to be drug products that diagnose, treat, cure, or prevent any disease or condition. These products have not been approved by the FDA, and the statements in this presentation have not been evaluated by the FDA. SkinMedica Daily Physical Defense Sunscreen Broad Spectrum SPF 30+ and TOTAL DEFENSE + REPAIR Broad Spectrum Sunscreens (SPF 34, SPF 34 Tinted, and SPF 50+) are over-the-counter drug products that are formulated and marketed pursuant to the FDA s governing regulations set forth at 21 CFR 352. Distributed in the U.S.A. by Allergan, Irvine, CA 92612 2016 Allergan. All rights reserved. All trademarks are the property of their respective owners. Patented. See: www.allergan.com/products/patent_notices Allergan.com SkinMedica.com 160090 37 16