AIVITA Biomedical Root of Skin Product Line. April 2018

Transcription

1 AIVITA Biomedical Root of Skin Product Line April 2018

2 AIVITA Biomedical Cancer Immunotherapy Technology Current Indications Mechanism Of Action Autologous Dendritic Cells Loaded With Tumor-Associated Antigens From An Autologous Short-term Cell Line Metastatic Melanoma Advanced Ovarian Cancer Glioblastoma Multiforme Fully Determined Immune Response Against Cancer Stem Cells, Specific For Each Individual ROOT OF TM Brand Technology Active Programs Current Products A revolutionary, clinically validated actives complex sourced from stem cells with applications in skincare, hair, and more. ROOT OF SKIN TM ROOT OF HAIR TM 2 Skincare Lines 6 SKUs All proceeds from the sale of ROOT OF SKIN TM support the treatment of women with ovarian cancer 2

3 AIVITA s Skincare Technology AIVITA s skincare formulations are developed in-house by a team that has pioneered stem cell treatments for spinal cord injury, motor neuron disorders, vision loss, and cancer. Stem Cell Media Specialized, proprietary, defined Skin Stem Cells Human stem cells are matured Growth Factors Sourced from human skin stem Products Two skincare lines, retail and stem cell media into skin progenitor cells cells, the very cells that make skin medical dispensed during development 3

4 AIVITA s Skincare Technology Developed in-house, made possible through world-class capabilities in cell therapy development Only product which captures every factor relevant to human skin development and health Only product which can mimic the supporting microenvironment of young, healthy skin Two clinical studies completed, and they both demonstrated robust efficacy and safety Multiple biological and histological studies completed, confirming clinical outcomes cgmp manufacturing methods and processes, with very low cost of goods Deep scientific characterization with peer reviewed publications 4

5 Product Overview ROOT OF SKIN TM A revolutionary line of skincare products containing AIVITA s clinically validated actives complex sourced from skin stem cells. Addresses visible signs of aging. Products Channels Revitalizing Face Renewal Serum - $55 Revitalizing Tinted Renewal Primer - $57 Revitalizing Eye Renewal Lotion - $48 Online Retail MLM (China) Markets US China Japan Korea ROOT OF SKIN TM MD A premium, luxury line containing twice the concentration of AIVITA s actives complex. Available through authorized professionals. Products Channels Face Serum - $180 ($90 wholesale) Tinted Moisturizer - $190 ($95 wholesale) Eye Complex - $120 ($60 wholesale) Professional Markets US Japan AIVITA Biomedical is developing a hair growth technology based on the same principles which enabled its skincare technology 5

6 Mechanism of Action: Contains ALL Factors Relevant to Skin Growthfactors Bone morphogenetic protein 5 (BMP-5) Collagen, type I Epidermal growth factor (EGF) Fibroblast growth factor (FGF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Growth differentiation factor 15 (GDF-15) Growth hormone (GH) Hepatocyte growth factor (HGF) Heparin binding epidermal growth factor Insulin-like growth factor and binding proteins 1 and 2 (IGF, IGF-BP1) Keratinocyte growth factor (KGF) Placenta growth factor (PGF) Platelet-derived growth factor-aa, and receptors (PDGF-AA) Role in skin biology Regulates number and size of keratinocytes Part of skin ECM Most potent mitogen of fibroblasts and keratinocytes Induces proliferation of fibroblasts and keratinocytes. Induces collagen synthesis in dermis Secreted by keratinocytes shortly after injury to induce wound healing Cytokine for fibroblasts in skin Regulation of keratinocyte differentiation Induces growth of keratinocytes and fibroblast Induces wound healing Involved in tissue regeneration and wound healing Mitogen for fibroblasts and keratinocytes Mitogen for fibroblasts and endothelial cells Stimulates re-epithelization and hair growth Mitogen for fibroblasts and promotes growth of endothelial cells Induces fibroblast migration and matrix production

7 Dermatologist Led Clinical Studies patients Clinical studies performed by world-renowned, board-certified dermatologist Zoe Draelos, MD Fellow of the American Academy of Dermatology Consulting Professor of Dermatology at DukeUniversity Principal investigator on over 400 clinical studies, author of over 350 publications, 40 book chapters and 8 books

8 Clinical Study Double-blind, 4-arm, 12 week clinical study of 100 female subjects, Fitzpatrick skin types with mild to moderate facial wrinkles Twice daily topical application to the face for a total of 12 weeks Endpoints include: tolerability, histological evidence of increases in skin matrix, demonstrated improvement in lines/wrinkles, safety Investigator assessed efficacy parameters (5 point ordinal scale): lines/wrinkles, firmness, radiance, skin texture, overall appearance Bio-measurements and assessments included: Transepidermal Water Loss (TEWL), Corneometry, Colorimeter, HD photography Percentage Score Improvement Over Baseline 70% 60% 50% 40% 30% 20% 10% 0% Week 2 Week 4 Week 8 Week 12

9 Dermatologist s Overall Assessment 100% * * * * Percentage Score Improvement Over Baseline 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% ** * * * * * Week 2 Week 4 Week 8 Week 12 * Wrinkles Deep wrinkles Tone Clarity Redness Roughness Fine line wrinkles Softness Roughness,softness Radiance * P 0.05

10 Clinical Study Results Trans-epidermal Water Loss (TEWL) is a Measurement of Skin Barrier Functionality Increase in TEWL is indicative of skin damage or pathological conditions of the skin TEWL is affected by environmental factors and the moisture content of the skin (hydration) Progressive and statistically significant decrease in TEWL from baseline Trans-epidermal Water Loss (TEWL)

11 Clinical Study Results Dermatologist Assessed Wrinkles, Skin Firmness, Radiance, Skin Texture Progressive and statistically significant improvement in all categories from baseline

12 Clinical Study Results 60% 50% 40% 30% 20% Overall Assessment by Investigator Week 2 Week 4 Week 8 Week 12 Dermatologist Evaluation of General Appearance and Integrity of Facial Skin Longitudinal intragroup analysis showed statistically significant improvement in overall appearance by week 2 Statistically significant improvementin wrinkles, radiance, texture, softness continued to week 12 10% 0% hesc-s hesc-f IPS-S IPS-F

13 Overall Assessment: Raw Data Wilcoxon Signed Ranks Test within groups for overall scores assessment by investigator at different time points against baseline Group Week 2 Week 4 Week 8 Week 12 hesc-s hesc-f IPS-S Z Asymp. Sig. (2-tailed) Z Asymp. Sig. (2-tailed) Z Asymp. Sig. (2-tailed) Longitudinal intragroup analysis showed statistically significant improvement in overall appearance by week 2 Statistically significant improvementin wrinkles, radiance, texture, softness continued to week 12 IPS-F Z Asymp. Sig. (2-tailed)

14 HD Photography Left Image = baseline Right image = 12 weeks later

15 HD Photography Subject 44

16 HD Photography Subject 109

17 HD Photography Subject 12

18 HD Photography Subject 104

19 HD Photography Subject 104

20 HD Photography Subject 55

21 HD Photography Subject 55

22 Summary of Main Clinical Study Application for 12 weeks was well tolerated, with improvement in every parameter evaluated Investigator reported all formulations improved lines/wrinkles, firmness/elasticity, radiance, skin texture/smoothness and overall appearance Bio-measurement assessment for TEWL showed statistically significant improvement as early as week 2, sustaining through week 12 No adverse effects Results of the 100-patient study concurred with those of the 8-patient pilot study

23 Histological Evaluation Skin biopsies* from each subject from the control (untreated) and treated study arm After 12 weeks, bi-daily application Biopsies were analyzed by pathological histologist for: Morphology of the cells and tissue, nuclear counts and presence/absence of abnormal structures Immunocytochemical expression of filaggrin, aquaporin, retepeg and collagen All samples processed in a blinded fashion * Biopsies from face are not allowable by IRB. Biopsies from behind the ear are painful and the morphology is different from the face. Upper arm skin has comparable sun exposure and morphology and was recommended by the dermatologist.

24 Histological Evaluation: Rete Peg Control Treatment Stratum Basale/ Stratum Granulosum Ratio Control Treated v Rete peg was significantly (p=0.038) increased in skin of treated subjects Rete peg was calculated as the ratio between thickness of basale and granulosum layers. Averages between treated and control biopsies were compared using paired t-test um

25 Histological Evaluation: Filaggrin Control 100 Treatment Filaggrin positive area (%) Control Treated v Expression of filaggrin was increased significantly (p= ) in treated skin Filaggrin was calculated considering the stained area and the intensity pixel value. Averages between treated and control biopsies were compared using paired t-test um

26 Histological Evaluation: Aquaporin Control AQP3 % Presence in Treatment vs. Matched Controls Treatment % medium and high intensity staining Control Treated v Expression of aquaporin was visually significant, but low sampling limited statistical significance Aquaporin was calculated considering the stained area and the intensity pixel value. Averages between treated and control biopsies were compared using paired t-test.

27 Histological Evaluation: Collagen

28 Summary of Histological Analyses Statistically significant increases in rete peg, filaggrin and collagen Rete pegs are structures at the dermal/epidermal junction which decrease in aging skin Filaggrin protects the skin and decreases with age Collagen increases structural integrity Indicates an improvement in skin barrier, skin quality and skin architecture Positive trending in nuclear counts in the stratum basale and spinosum layers of the epidermis, and Aquaporin Suggestive that skin is more actively regenerating in treated samples compared to matched controls

29 Conclusion Product mimics human skin microenvironment, containing every factor relevant to human skin development and health Two clinical studies completed, and they both demonstrated robust efficacy and safety Multiple biological and histological studies completed, confirming clinical outcomes cgmp manufacturing methods andprocesses, with very low cost of goods Deep scientific characterization phenomenal outcome, revolutionary product, better than retinols, and without the injury

30 Clinically Validated Skincare In vitro efficacy was tested in a 3D model of human skin. The results demonstrated an increase in skin-barrier and structural proteins, as well as collagen I & III after five days of exposure 3D skin model exposed to SourceCode Technology TM, ROOT OF SKIN TM s active ingredient. Shows a thin, compact stratus corneum along with enhanced cellularity of the epidermis that clinically translates to improved hydration, water retention, better protection from environmental aggression, accelerated healing potential, and improved appearance: reduced wrinkles, smoothness and an amazing pearlescent radiance. 30

31 Skincare Market Opportunity The global skin care market is estimated to be $134.5 billion in Market Share by Channel in the United States Sales Share of the Leading Brands in the United States for Medical Care Providers Sales Share of Take-Home Skin Care Products by the Direct Sales Subclass in the US *Professional Skin Care: U.S. Market Analysis and Opportunities - January 2016 Kline Report 31

32 Financial Security and Marketing Advantage Proceeds from the sale of ROOT OF SKIN TM support the treatment of women with ovarian cancer

33 AIVITA Biomedical, Inc Von Karman Ave. Irvine, CA T / F