[ 영문 ] Time for Skin Immunity DOCTORS PGA

[ 영문 ] Time for Skin Immunity DOCTORS PGA

01. BioLeaders Bio-drug development for next generation immunotherapy Technology Verification and Leaping Period 2016. 07 Listed in KOSDAK market 2016. 04 Joint development of uterine cervical cancer medicine and Technology transfer agreement with Jeil Pharmaceutical 2016. 03 Completed Clinical Phase 2a of uterine cervical cancer medicine 2015. 12 Completed Clinical Phase 2b of CIN1 medicines 2015. 06 Completed Clinical Phase 1 of uterine cervical cancer medicine 2014. 11 Listed in KONEX market 2012. 08 Agreement with GREEN CROSS for Joint development of CIN1 medicine 2012. 01 Coompleted Clinical Phase 1 of CIN1 medicine Building a Biz Base 2005. 12 Investment Invitation & Joint Tech. Development Agreement with GREEN CROSS 2000. 07 Corporate R&D Institute acknowledged by Korea Industrial Tech. Association 1999. 12 Established BioLeaders Co., Ltd. Securing Source Technologies 2011. 11 Clinical Phase 1 of CIN1 medicine approved by FDA 2008. 07 Established Japan Branch in Osaka 2007. 12 Selected as one of Korea 10 New Technologies and awarded the Grand Prize of Technology (Mass production technology for weight, Poly-γ-glutamic acid) 2007. 08 New technology NET certified (Medicine material development technology using high molecular weight, Poly-γ-glutamic acid) 사내교육용 (Internal Use Only) 2

01. BioLeaders Source technology to develop next generation immunity medicine New bio-medicine development for next generation immunotherapy 01Recombinant protein - Interluekin - Interferon - Chemokine - Growth factors 02 Vaccine - Bacterial vaccine - Virus vaccine - Recombinant vaccine 03 Immunity medicine - Gene medicine - Cell medicine - Antibody medicine Next generation immunity medicine technology (MucoMax TM & HumaMax TM ) Verification pipeline of Clinical effectiveness Uterine cervical cancer medicine(bls-ilb-e710) CIN1 medicine BLS-PGA-C10) Verification pipeline of Clinical effectiveness Muscular dystrophy medicine (BLS-ILB-MD1) Anticancer immuno-therapeutic agent (BLS-M101, M102) Anti-metabolic medicine (BLS-M201, indication : hyperlipidemia) Immune disorder medicine (BLS-H101, indication : atopy, rhinitis, etc.) Verification pipeline of Clinical effectiveness Extendability : All immunotherapic target diseases Safety : Materials of new medicine harmless to human body Easy medication : Oral administration 사내교육용 (Internal Use Only) 3

02. DOCTORS PGA DOCTORS PGA FOR YOUR SKIN What is Poly-γ-glutamic acid (γ-pga)? A substance connected in the form of gamma combination of glutamic acid, a kind of amino acid. A biomaterial produced from the microbe, Bacillus subtilis, in GRAS fermented food A high polymer of the functional natural amino acid contained in the sticky mucous substance of rich soybean paste Amino acid polymer (Combination of gamma and peptide) Polymer material Biological safety Biodegradability Water solubility 사내교육용 (Internal Use Only) 4

02. DOCTORS PGA Mechanism of γ-pga DOCTORS PGA FOR YOUR SKIN Push and Pull Ability of γ-pga Cosmetic Brand DOCTORS PGA with the main material of γ-pga Push bad things, Pull good things Skin Care Solution, Push & Pull DOCTORS PGA is a premium brand, that pulls minerals and water including calcium beneficial to skin, strengthens weak skin barrier, pushes and blocks various harmful factors including fine dust, and helps prevent skin damage and improve skin. Application of Poly-gamma-glutamic acid (γ-pga) to cosmetics is intended to push bad things like harmful substances or fine dust, to pull good things like water or wound recovery, and to normalize skin immunity. Push Harmful microbes Allergy causing substances Inflammation Photoaging and wrinkle Fine dust Pull Water Elasticity Minerals Wound recovery 사내교육용 (Internal Use Only) 5

02. DOCTORS PGA Mechanism of γ-pga DOCTORS PGA FOR YOUR SKIN Push and Pull Ability of γ-pga Push bad things (Push) Pull good things (Pull) Bacterial cell Allergen Photoaging, wrinkle Inflamma tion Fine dust γ-pga γ-pga Water Elasticity Ca 2+, Mg 2+ Mn 2+, F + Wound recovery As γ-pga has (-) charges, it pulls viruses or allergens with (-) charges. Besides, it covers water film over skin and protect skin from irritation like fine dust. As γ-pga has strong hygroscopic and moisturizing properties, it absorbs water in the air and prevents water loss in skin. Besides, it has (-) charges and prevents loss of inorganic substances like calcium having (+) charges. 사내교육용 (Internal Use Only) 6

02. DOCTORS PGA Mechanism of γ-pga DOCTORS PGA FOR YOUR SKIN Functional cosmetic material : γ-pga High molecular weight γ-pga Molecular weight: Over 2 million Da, 15,000 residues of Glu Low molecular weight γ-pga Molecular weight: 1,000 Da, Glu 8 residue 250 Viscosity (cp) 200 150 100 50 0 10 50 500 1,000 2,000 PGA molecular weight(kda) Epidermis Dermis Low molecular weight γ-pga [glu 8 residue] High moisturizing material Functional material for antiphotoaging and wrinkle repair through skin penetration 사내교육용 (Internal Use Only) 7

02. DOCTORS PGA DOCTORS PGA FOR YOUR SKIN Mechanism of γ-pga Improves water holding ability of dermis through inhibition of Hyaluronic Acid(HA) degradation Inhibitive function of the Hyaluronidase activity of the human body derived substance, Hyaluronic Acid (HA) of low molecular γ-pga 120 100 80 If inflammation develops, hyaluronidase is activated, destructing tissue structure, accelerating inflammatory cytopermeability. Enhances hyaluronic acid stability through inhibition of Hyaluronidase Antiinflammatory function through inhibition of Hyaluronidase activity 60 40 20 0 0 0.002 0.004 0.006 0.008 [Patent] Hyaluronidase inhibitor containing polygamma-glutamic acid as an effective ingredient - Korea Patent Registration No.0582120(2006.05.15) - Japan Patent Application 2006-002645 (2006.01.10) Review of anti-allergic action of Japanese larch and effectiveness on apotic dermatitis Japan Pharmacological Joournal (Folia Pharmacol.Jon) 124:271-283 (2004) - US Patent 12/090,678 (2008.04.18) - Europe Patent 05 804 510.5 (2008.04.14) - China Patent 200580051876.8 (2008.04.18) - Canada Patent 2,627,454 (2008.04.21) 사내교육용 (Internal Use Only) 8

02. DOCTORS PGA DOCTORS PGA FOR YOUR SKIN Mechanism of γ-pga Decreasing effect of Trans-Epidermal Water Loss Efficacy evaluation test result for human body showed transepidermal water loss was decreased compared with other moisturizing substances, hyaluronic acid and collagen. Laboratory : Kyung Hee University Skin Biotechnology Center / Test subject : Women aged 28-51 사내교육용 (Internal Use Only) 9

02. DOCTORS PGA DOCTORS PGA FOR YOUR SKIN Mechanism of γ-pga γ-pga as a real moisturizing substance Skin Moisturizing Underlying skin moisturizing and protective function To interrupt external irritant, it is important to fill stratum corneum with intercellular lipid. Especially for atopic skin, intercellular lipid in widely open stratum corneum can be lost easily. γ-pga Strengthens skin barrier, preventing loss of intercellular lipid. Activates Natural Moisturizing Factors (NMF), helping water supply and retention in stratum corneum. 사내교육용 (Internal Use Only) 10

02. DOCTORS PGA γ-pga as Cosmetic Ingredient DOCTORS PGA FOR YOUR SKIN Recovery of Skin Barrier = Recovery of Skin Immunity Stratum Corneum Tightens stratum corneum, improves keratin structure and state, and normalizes regeneration and barrier functions through normal expoliation. Epidermis 19% dermis increase by recovering skin moisture retention function Dermis Increases a fundamental substance (Glycosaminoglycan) up to 49-51% Recovery of skin barrier Recovery of skin immunity Selective skin permeability is maintained * Selective permeability : Healthy skin has selective permeability that prevents inflow of substances harmful to skin and receives beneficial elements only. 사내교육용 (Internal Use Only) 11

02. DOCTORS PGA γ-pga as Cosmetic Ingredient DOCTORS PGA FOR YOUR SKIN γ-pga works in skin, decreases trans epidermis water loss, and eventually helps restore Skin Barrier. Stratum Corneum γ-pga, high moisturizing effect - 100 times hygroscopicity of HA(hyaluronic acid) - Intercellular lipid loss prevention by water film - Promotes immunity cell differentiation process. Epidermis γ-pga, skin immune action - Acts on Langerhans cell, T-cell in the epidermis. - Promotes immunity cell differentiation process. Dermis γ-pga, skin elasticity, anti-inflammation - Inhibition of hyaluridase activity - Stability increase of hyaluronic acid, anti-inflammatory function 사내교육용 (Internal Use Only) 12

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Clinical Test of γ-pga Skin moisture improvement Improvement of skin keratinization Before use Before use 4 weeks 4 weeks 8 weeks 8 weeks The graph shows skin moisture improvement. The higher the value, the more skin moisture. The graph shows the change of skin keratinization. The lower the value, the less skin keratinization. Dermal moisture improvement Improvement of trans-epidermal loss Before use Before use Skin clinical test result by Korea Institute of Dermatological Sciences 1. Test period: 2016/1/20 ~ 2016/3/16 (8 weeks) 2. Subjects: 24 men & women aged 5~41 with mild or severe atopic skin 3. Test product: DOCTORS PGA Deep Care Moisturizing Cream 4 weeks 8 weeks The graph show skin moisture improvement rate. The higher the value, the more skin moisture. 4 weeks 8 weeks The graph shows skin moisture improvement rate. The higher the value, the more skin moisture. 사내교육용 (Internal Use Only)

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Clinical Test of γ-pga Skin redness improvement Improved atopy visual evaluation Before use Before use 4 weeks 4 weeks 8 weeks 8 weeks The graph shows skin redness change. The lower the value, the more skin soothes. The graph shows SCORAD index improvement rate. The higher the value, the more symptom improves in atopy visual evaluation. Itching relief by dry Safety evaluation completed Skin clinical test result by Korea Institute of Dermatological Sciences 1. Test period: 2016/1/20 ~ 2016/3/16 (8 weeks) 2. Subjects: 24 men & women aged 5~41 with mild or severe atopic skin 3. Test product: DOCTORS PGA Deep Care Moisturizing Cream Before use 4 weeks 8 weeks The graph shows the severest itching. The lower the value, the less skin itching by dry Excluding ingredients irritant to skin, safety evaluation result by skin patch test revealed that average skin reaction was 0.00. Thus the product was judged no irritation according to acceptance criteria. Test period: Korea Institute of Dermatological Sciences Test Period : 2016.01.25~2016.01.29 Subject: 33 men and women Test product: DOCTORS PGA Deep Care Moisturizing Cream 사내교육용 (Internal Use Only)

03. DOCTORS PGA Products Clinical Test of γ-pga DOCTORS PGA FOR YOUR SKIN Visual evaluation by atopy diagnostic criteria/ Before & After Skin Moisturizing Skin keratinization Atopic dermatitis symptom area Atopic dermatitis symptom area Skin clinical test result by Korea Institute of Dermatological Sciences 1. Test period: 2016/1/20 ~ 2016/3/16 (8 weeks) 2. Subjects: 24 men & women aged 5~41 with mild or severe atopic skin 3. Test product: DOCTORS PGA Deep Care Moisturizing Cream 사내교육용 (Internal Use Only)

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Deep Care Moisturizing Cream (Another name, Push-Pull Cream) 50 ml High moisturizing, skin carrier reinforcing cream, containing high concentration poly-γ-glutamic acid, centella asiatica leaf extract, tea tree extract, and propolis, easy to dry, providing intensive care for sensitively reacting skin Deep care solution for sensitive skin Completed human skin verification test for ages 5-41 (skin moisture improvement, keratin decrease, skin soothing, itching relief were identified) Contains vegetable extract for skin health. Fresh touch high moisturizing cream Weak acid formula of ph5.6 사내교육용 (Internal Use Only) 16

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Deep Care Repairing Spot Cream 20 ml Intensive care cream for local areas, helping damaged skin circulation by gently wrapping sensitive skin barrier with high concentration poly-γ-glutamic acid, a cell growth factor EGF, centella asiatica leaf extract, tea tree extract, and propolis Deep care solution for sensitive skin due to frequent practices Contains EGF and ceramide helping the recovery of damaged skin. Contains vegetable extract for skin health. A formula excellent in application, absorption and adhesion Spot cream of convenient multi-functions 사내교육용 (Internal Use Only) 17

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Deep Care Eye Lifting Cream 15 ml Wrinkle repair functional eye cream taking care of loose skin smoothly and elastically, containing high concentration poly-γ glutamic acid (γ-pga), acetyl hexapeptide, dipalmitoyl hydroxyproline, and other functional ingredients, providing strong moisturizing effect for and acting on the aging trouble areas 360 elastic care for aging loose skin Excellent formula without lumping and being pushed Skin stream correction and brightening care Deep care solution for sensitive, dry area Contains centellar asiatica extract and various vegetable extracts helping the recovery of damaged skin. 사내교육용 (Internal Use Only) 18

03. DOCTORS PGA Products DOCTORS PGA for your skin Deep Care Reviving Ampoule 10 ml X 7 ea This is an ampoule that brightens your skin tone and makes its texture firmer with brightening and wrinkle smoothing functions. It contains Poly-gamma Glutamic Acid (γ-pga), EGF, Ceramide, etc., and it gently permeates your skin to provide moisture and soothing care even to the deeper layer of dry, sensitive skin. Deep care solutions for sensitive skin caused by frequent cosmetic procedures Contains various nutrients including EGF and ceramide Soothing, moisturizing care for irritated skin Brightening and wrinkle smoothing ability for dull and sagging skin 사내교육용 (Internal Use Only) 1.

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Multi Peptide V-Serum 110 ml It's a whitening and wrinkle-improving serum that supplies moisture by penetrating deep into the skin with its fine bubbles that appear after skin application. It also nourishes the skin that has lost elasticity and vitality with poly-gamma glutamic acid (γ-pga), marine collagen, peptide complex and volufiline to promote vitality. Exceptional whitening and lifting care solutions for a variety of skin aging Effective moisturization with bubbles that appear when applied to the skin Contains marine collagen, peptide complex, and volufiline Conditioning and skin texture improvement through skin vitality enhancement Whitening and wrinkle-improving functionality for dull and sagging skin 사내교육용 (Internal Use Only) 20

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Special Care UV Protecting Sunblock 50 g Light touch sunblock adhered to skin without turbidity, stickiness and greasiness, where high moisturizing ingredient poly-γ-glutamic acid forms water film, keeps dry skin moist, blocks harmful UV, and protects sensitive skin Special care solution for UV-sensitive skin Moist and soft formula for sensitive skin due to frequent practices Triple functional cosmetics (UV block, whitening, wrinkle repair) Turbidity and stickiness Non-greasy, light touch 사내교육용 (Internal Use Only) 21

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Daily Care Hydrating Foam Cleanser 120 g A foam cleanser of a whipping type completely cleansing wastes accumulated in skin due to the external environment; A foam cleanser without skin tightening containing poly-γ-glutamic acid and forming water film with more moist, soft foam Daily care solution for sensitive skin to external environment Gentle cleansing with foams of a whipping type A soft formula with irritant ingredients minimized Moist foam cleanser with less tightening after use 사내교육용 (Internal Use Only) 22

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Daily Care Soothing Mist 120 ml Soothing mist with poly-gamma glutamic acid and various moisturizing factors that calms the skin stimulated from the harmful environment and gives care to result in a fresh and clear skin. Daily care solution that grants moisturization every day Mild formula that minimized stimulants Patented ingredients, such as Phyto-Oligo and Centella, included for skin soothing effects (Phyto-Oligo: Patent register no. 10-0887294, mucilage material which is separated from low temperature extract from safflower and aloe. It has excellent moisture retention, anti-inflammation and skin soothing effect.) Neat type that does not leave stickiness after use 사내교육용 (Internal Use Only) 23

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Daily Care Hydrating Lotion 140 ml This is a non-sticky, hydrating lotion that provides a refreshing feeling. It protects dry and sensitive skin with a layer of moisture consisting of highly hydrating Poly-gamma Glutamic Acid, Epidermal Growth Factor (EGF) and Ceramide. Daily care solution providing everyday moisturization Mild formula with minimal irritation Contains EGF and ceramide for skin health Non-sticky with a refreshing feeling 사내교육용 (Internal Use Only) 2.

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Daily Care Moisturizing Mask Pack 24 g X 10 ea A mask pack, where poly-γ glutamic acid (γ-pga) provides strong moisturizing effect, containing various nutrients like EGF and ceramide, forming tight skin barrier over the sensitive skin to external environment, giving vitality and elasticity, helping keep moisture for a long time Daily care solution for sensitive skin to external environment Contains EGF, ceramide and various nutrients Immediate soothing, moisturizing care for irritated skin Daily care mask pack with no burden in spite of daily use 사내교육용 (Internal Use Only) 25

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Moisturizing Mask Pack 24 g X 10 ea A mask pack, where poly-γ glutamic acid (γ-pga) provides strong moisturizing effect, containing various nutrients like EGF and ceramide, forming tight skin barrier over the sensitive skin to external environment, giving vitality and elasticity, helping keep moisture for a long time Micro Fiber Cellulose Sheet Mask Pack Using Cloudcell Contains EGF, ceramide and various nutrients Immediate soothing, moisturizing care for irritated skin Daily care mask pack with no burden in spite of daily use 사내교육용 (Internal Use Only) 26

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Micro Fiber Cellulose Sheet Mask Pack Using Cloudcell Cloudcell : High Wet Modulus Transparent Fine Rayon Staple Fiber Composition - Denier : 1.2 ± 4% - Fiber Length : 40mm ± 3% - Moisture Regain : 13% [Cloudcell rayon fiber] [normal rayon fiber] 사내교육용 (Internal Use Only) 27

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Micro Fiber Cellulose Sheet Mask Pack Using Cloudcell Feature - The concave on the fiber surface is about 1/10 than normal rayon fiber, cause no burden to the skin. - The fiber perfectly fit the skin due to great fitness 1.3 times better than normal rayon fiber. - Good for skin moisturizing due to penetration ability 1.5 times superior to normal rayon fiber. - Although it's finer fiber, the strength is still guaranteed with cross fiber entanglement. Strength is 1.6 times better than normal rayon fiber. - It gets transparent when wet. 사내교육용 (Internal Use Only) 28

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Secret Cure Mist 25 ml Contains a patent material poly-γ glutamic acid(γ-pga), wormwood, portulaca oleracea extract, and other vegetable extracts, reinforcing skin barrier of weak and sensitive areas of a woman, helping keep weak acid ph for healthy skin balance. Besides, it is a mist type women s product, improving dull skin tone, giving freshness with delicate lavender scent. A solution to take care of women s sensitive area Weak acid ph formula for healthy skin balance Taking care of offensive odor with delicate lavender scent Whitening functional product to improve dull skin tone. 사내교육용 (Internal Use Only) 29

03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Secret Cure Mist : GPGA: Anti-virus function through mucosal immunocyte irritation Antiviral Res. (2012) 94:98 Induction of type I interferon by high molecular poly-g-glutamate protects B6.A2G-Mx1 mice against influenza A virus. - Inhibition of virus replication - Identification of virus clearance - Survival rate increase against highly pathogenic virus infection [Operating mechanism] Administer poly-γ glutamic acid into the nosal cavity Irritates immunocytes in the nasal mucosa. Irritated immunocyte increases secretion of IFN-beta, a cytoki ne, having an anti-virus function (inhibition of virus infection, viru s infection and apoptosis ) Prevents virus infection and kills virus-infected cells [Patent] A composite containing poly-γ glutamic acid to inhibit virus infection (Korea Patent No. 0873179) 사내교육용 (Internal Use Only) 30

Antiviral activity (%) 항바이러스활성 (%) 03. DOCTORS PGA Products DOCTORS PGA FOR YOUR SKIN Secret Cure Mist : Check antiviral activity of GPGA 1. Test method : Antiviral activity test method using fertile eggs 2. Test specimen 1) Test specimen : Secret Cure Mist (base ingredient, GPGA not included), Secret Cure Mist (GPGA included) 2) Control specimen : Summer s Eve Feminine Cleansing Mist No. Test specimen virus concentration (EID) in Allantoic fluid Antiviral activity Remarks 100 99% 99% inhibition 바이러스 of virus infection 감염억제 1 Control (non treated) 1 X 10 5.5 EID 50 /ml - 80 2 3 Secret Cure Mist (base ingredient) Secret Cure Mist (GPGA included) 1 X 10 5.25 EID 50 /ml 43.8 % 1 X 10 3.5 EID 50 /ml 99 % The number of viruses decreased by 1.78 time s compared with that of Control specimen The number of viruses decreased by 100 time s compared with that of Control specimen 60 40 20 4 Summer s Eve Feminine Cleansing Mist * EID : embryo infective dose 1 X 10 5.5 EID 50 /ml - 0 Control (non treated) 시크릿 Secret 큐어 Cure 미스트 Mist (base (base 성분 ) ingredient) 시크릿 Secret Cure 큐어미스트 Mist (g-pga (γ-pga 함유 ) included) Summer s eve 사내교육용 (Internal Use Only) 31

Thank You! 사내교육용 (Internal Use Only) 32