Recombinant Human Epidermal Growth Factor Easyef® Ointment Recombinant Human Epidermal Growth Factor

Easyef® Ointment General Information What is EGF? Epidermal Growth Factor (EGF) is a single-chain polypeptide consisting of 53 amino acids with a molecular weight of about 6,200 Daltons. Six cysteine residues in the sequence of hEGF from three disulfide bonds are required for hEGF to be biologically active. EGF was first isolated from the submaxillary glands of adult male mice. Human EGF was discovered in human urine as an inhibitor of gastric acid secretion. Today, hEGF has become one of the most attractive growth factors in life sciences as well as biotechnological fields. Human EGF is a potent stimulator of epithelial and endothelial cells and fibroblast proliferation both in vitro and in vivo, which results in its potential as a promising healing agent for the treatment of various skin and corneal wounds. In dermatology, EGF can be used as a healing agent for skin wounds, such as diabetic ulcers, bed sores, venous stasis ulcers, skin burns and surgical incisions. In ophthalmology, EGF can be utilized as a healing agent for corneal ulcers and ophthalmic surgery, such as corneal transplantation and excimer laser keratectomy, and the prevention of corneal degeneration. It is also a good candidate for the treatment of gastric ulcers because it inhibits gastric acid secretion and regenerates gastric mucosal layer. 1

Easyef® Ointment Mechanism of EGF Action 1. Re-epithelialization EGF promotes epithelial cells to proliferate and move to fill wounds. 2. Promotion of granulation tissue EGF stimulates fibroblasts in dermal tissue to facilitate dermal cells to differentiate and proliferate. 3. Angiogenesis EGF promotes endothelial cells to proliferate to regenerate blood vessels. 2

Skin Regeneration and the Healing Effect Easyef® Ointment Skin Regeneration and the Healing Effect 1. Non-clinical study Skin regeneration rate (%) Duration of treatment (Days) C product Easyef® Ointment Completely healed in about 9.8 days in about 7.8 days Full-thickness wound model in the pig Wound size/depth: 4 x 4 cm, 0.05 mm Administration and period: twice a day (0.4 g applied per administration), treated for 11 days Ref) The Journal of the Korean Dermatological Association 1995 2. Clinical study ► Indication: Wound healing (Skin graft donor site model) ► Methodology: Placebo-controlled, randomized, double-blind, multi-center study ► Primary endpoint: Healing time by the direct evaluation(naked eye) of skin graft donor site ► Result: The test group displayed statistically significant 1.0 day faster healing time compared to the control group (p=0.0005). ITT N=64 PP N=61 Placebo EGF 1 μg/g Healing time (day) (mean±SD) 8.109±1.492 7.609±1.344 8.107±1.528 7.598±1.363 Healing time difference (day) median (min, max) 0.500±1.098 1.000 (-1.500, 3.500) 0.508±1.116 p-value 1) 0.0005 0.0007 95% confidence interval 0.500, 1.000 0.000, 1.000 1) Wilcoxon signed- rank test Outstanding effect of skin generation The wound applied with Easyef® Ointment demonstrated the quickest healing ability. Rapid wound healing ability The shortest healing time was achieved in the same wound area. 3

Key Benefits and Features Easyef® Ointment Key Benefits and Features Wound healing ointment with a new concept, containing EGF, a granulation ingredient (granulation tissue) in the human body, offered first in Korea. Safe because it contains no steroids or antibiotics. White blood cells or macrophages themselves, which are created during the healing process in our body, suppress bacteria, to some extent. Therefore, this medicine does not contain a steroid or an antibiotic of which the excessive use may make us tolerant of the antibiotic. Proven in its safety and healing effect through a clinical studies in Korea. Top medical staffs from three prestigious Korean Institutions (Asan Medical Center, Severance Hospital, and Samsung Medical Center) joined the clinical procedures, and approved the safety and remarkable healing effect of EGF. Table of Comparison with Competitors Product name Easyef® Ointment A B C API EGF (Epidermal Growth Factor) Sodium fusidate Mupirocin Centella asiatica extract Type No antibiotic No steroid Antibiotic Antibiotic, steroid Tolerance/ Side effect Same ingredient as in the human body (no side effect) Tolerance (antibiotic) Side effect (steroid) Efficacy/ Effect Assistive topical treatment of wound and skin ulcer Pyoderma, acne, folliculitis, boil, and secondary infection due to a burn and wound Bacterial skin disease   Skin inflammation, infected wound Storage Store in a refrigerator (2~8℃) Room temperature (1~30℃) 4

Easyef® Ointment Product Information Component In 1 g Recombinant human epidermal growth factor ------------------------------ 1 μg (Host: E. coli JM101, Vector: pTE105) Ointment base: white petrolatum (KP) ------------------------------------ 700 mg Ointment base: Light liquid paraffin (KP) ----------------------------- 298.45 mg Preservative: propylparaben (KP) ------------------------------------------- 1.5 mg Appearance Colorless or pale yellow, translucent ointment in tube Administration/Dosage Apply it to the infected area several times a day as needed. Efficacy/Effect Assistive topical treatment of wounds and skin ulcers Storage Store in a refrigerator (2~8℃).

Easyef® Ointment Release Date : 2010.12.30 http://www.daewoong.com For More Information Contact: Chang-woo Suh Tel: 82-2-550-8737 E-mail: cwsuh@daewoong.co.kr 163-3, Samsung-dong, Gangnam-gu, Seoul 135-715, KOREA