1. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation®: the only one US FDA approved alternative to injection Mattioli Engineering Mattioli Engineering

2. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® The only top No.1 technology alternative to injections

3. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® is a technology that allows product delivery into the various layers of the skin or subcutaneous tissues. Dermoelectroporation® is a technology that allows product delivery into the various layers of the skin or subcutaneous tissues. Any water soluble ingredients can be inserted into the skin without additional carrying Gels. Any water soluble ingredients can be inserted into the skin without additional carrying Gels. Dermoelectroporation® utilizes the skin water based Dermoelectroporation® utilizes the skin water based channels to allow product penetration due to controlled current pulses delivered to the patient. Dermoelectroporation®

4. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering microdermabrasion leader since 1991 Mattioli Engineering microdermabrasion leader since 1991 Empowering Skin Care specialists across the world with revolutionary technologies to treat skin. Empowering Skin Care specialists across the world with revolutionary technologies to treat skin. Additional opportunities to further enhance delivery of active ingredients into the skin was sought. Additional opportunities to further enhance delivery of active ingredients into the skin was sought. Combining the concept of Meso therapy (by Dr. Pistor, 1952) and Mattioli Engineering’s technical expertise led to development of Dermoelectroporation. Combining the concept of Meso therapy (by Dr. Pistor, 1952) and Mattioli Engineering’s technical expertise led to development of Dermoelectroporation. Why Dermoelectroporation®

5. Copyright 2008 © Mattioli Engineering All rights reserved What Dermoelectroporation is not What Dermoelectroporation is not Microdermabrasion Microdermabrasion Galvanic Galvanic Ionthophoresis Ionthophoresis Ultrasound / Sonophoresys Ultrasound / Sonophoresys Aquaphoresys Aquaphoresys Massagers Massagers Laser device Laser device Transderm® is the ONLY and REAL alternative to injections.

6. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery Microdermabrasion Medical and Aesthetic application –1 st transdermal pathway –Skin surface action only –No current applied –Small sized molecules only –Low delivery rate

7. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies Existing Technologies Low Dc current level applied Traditional Galvanic (1to 5mA) Aesthetic application –Pushes ions into the skin. –Low Dc current level applied. –Ineffective for high weight molecules. –Pre-charged compounds needed. –Small sized molecules only. –Substance PH will change. –Electrolysis (product separation).

8. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery Traditional Pulsed Ionthophoresis (1to 5mA) Medical and Aesthetic application –Pushes ions into the skin. –Low Ac current level applied. –Ineffective for high weight molecules. –Pre-charged compounds needed. –Small sized molecules only. –Substance PH may change. –Electrolysis (product separation). Sinus Low Ac current level applied Alternative Low Ac current level applied

9. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery Electroporation In lab application only –Macromolecules delivery –High peak currents needed to porate the external skin layers (18,000volts) –High risk of permanent skin damage –Many Adverse effects High peak currents Ionthophoresys currents

10. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery High Frequency vibration 3MHz or higher Ultrasounds Medical and Aesthetic application –No current applied –High vibration frequency on the skin –Ineffective for high weight molecules –Small sized molecules only

11. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery High Frequency vibration Lower than 3 MHz Sonophoresys (Sound) Medical and Aesthetic application –Low frequency Ultrasound –Ineffective for high weight molecules –Small sized molecules only

12. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies for delivery Existing Technologies for delivery Aquaphoresys (1to 5mA) Medical and Aesthetic application –Ultrasounds + current stimulation –Low Ac current –High freq. Ultrasounds –Ineffective for high weight molecules –Small sized molecules only –Ionic drug solutions PH may change –Electrolysis (ionic separation) Low Ac current level applied

13. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® Is a Proprietary Patented Technology from Mattioli Engineering Engineering. The only US FDA Cleared Device as alternative to injections (Top n.1) Micro-molecules and MACRO-molecules are safely delivered. Using the skin ’ s water based “ channels ” (aquaporins). Low and controlled current pulses delivered to the skin No skin damage, no adverse effects, no contraindications No effect on the substance being inserted/ ” injected ”. Faster than traditional Ionthophoresis / Galvanic devices (same amount of product)

14. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® What the Technology is used for?

15. Copyright 2008 © Mattioli Engineering All rights reserved FOR EDUCTIONAL PURPOSES ONLY Dermatology treatments. Dermatology treatments. Skin rejuvenation and bio revitalization. Skin rejuvenation and bio revitalization. Cellulite treatments. Cellulite treatments. Fat deposits Fat deposits HyperHidrosis (Botulinum toxine administration) HyperHidrosis (Botulinum toxine administration) Acne pathologies. Acne pathologies. Hormone replacement treatments Hormone replacement treatments Pre laser treatments. Pre laser treatments. Pre and post plastic surgery sessions. Pre and post plastic surgery sessions. Replacing injections for Mesotharapy applications. Replacing injections for Mesotharapy applications. Transderm® Meso® System® Transderm® Meso® System®

16. Copyright 2008 © Mattioli Engineering All rights reserved FOR EDUCTIONAL PURPOSES ONLY Transderm® Meso® System ® Transderm® Meso® System ® Meso-Botulinum Toxine applications. Meso-Botulinum Toxine applications. Wrinkles treatments. Wrinkles treatments. Stretch mark treatments. Stretch mark treatments. Actinic Keratosis applications. Actinic Keratosis applications. Steroids applications Steroids applications Pain management Pain management Rheumatic and post rheumatic pathologies. Rheumatic and post rheumatic pathologies. Sports medicine (F.C. Juventus) Sports medicine (F.C. Juventus)

17. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® Who is this Top No.1 technology available for?

18. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® is available for: Skin Care Specialists that want to optimize the delivery of a high range of ingredients and not only a very few of them….. Clinics/salons that realize the limitation of conventional beauty treatments and want to offer additional treatments with a significant improvement in efficacy to move ahead off common level clinics / salon…...Providing a wide range of applications in only one device and/or improving existing protocols on use. Dermoelectroporation®

19. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Scientific principle

20. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® utilizes the skin water based channels to allow ionic drug solutions to penetrate due to controlled current delivered to the patient. (Dermoelectroporation® stimulates the opening of the existing water based channels to create a transdermal passage to deliver drugs deep into the derma.) Dermoelectroporation®

21. Copyright 2008 © Mattioli Engineering All rights reserved Scientific principle Reproduces transient changes in skin microstructure -Reproduces transient changes in skin microstructure -Current flowing through the extra cellular matrix (mainly composed by water, ions, and glycosaminoglycans) to make the -Long-chained glycosaminoglycans to,transiently, orient themselves to create “channels” (Water based ones) allowing the delivery of Macromolecules through the skin. No cell injury (i.e. fragmentation of cytoplasm or nucleus, abnormalities of plasma membrane due to low current intensity used). (V., Ruggiero, M., and Magnelli, L.: Angiogenesis and the unique nature of tumor matrix. Mol. Biotech. 21: 85-90, 2002.).

22. Copyright 2008 © Mattioli Engineering All rights reserved Cells Scientific principle

23. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Substances driven through

24. Copyright 2008 © Mattioli Engineering All rights reserved Transderm® Meso® System ® Transderm® Meso® System ® FOR EDUCTIONAL PURPOSES ONLY What substances are driven? Collagen Hyaluronic Acid Lidocaine L-Carnitine Vitamins Amino Acids Heparin Elastine Mesotharapy Procedures Glutathione Hormone Replacement Phosphatidylcoline Aminophylline Hyaluronidase MTE-4 Ionic skin tissue growth gel Steroids (Studies available from May 2007)Botulinum toxine (Studies available from May 2007) Growth Factors Lymidiral Veno-M Placentex Diclofenac And many other “cocktails”…..

25. Copyright 2008 © Mattioli Engineering All rights reserved Existing Technologies Existing Technologies Why Transderm has been indicated as alternative to injection

26. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Dermoelectroporation®: Delivery pulses principle

27. Copyright 2008 © Mattioli Engineering All rights reserved Delivery pulses principles Dermoelectroporation (0 - 5mA) Human use –Low and controlled current -No skin damage –Macro molecules deliverable –No adverse effects –No Contraindications –To be used on human beings Low and controlled current level applied

28. Copyright 2008 © Mattioli Engineering All rights reserved Dermoelectroporation® Dermoelectroporation® Practicing with Dermoelectroporation®.

29. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Dermoelectroporation is a 2 steps Procedure: It forsees a preventive Microdermabrasion to reduce the skin impedance and to optimize the use of Transderm® Meso® System ® for transdermal delivery of products

30. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution

31. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Dermoelectroporation®: Features,Advantages & Benefits

32. Copyright 2008 © Mattioli Engineering All rights reserved Features of Dermoelectroporation® -Capability to transdermally deliver ionic drug solutions -Capability to transdermally deliver both micro and macromolecules (greater than 800,000Dalton) -No electrolysis of ionic drug solution or variation in the ionic drug solution pH -Both positive and negative ions of the drug are transdermally delivered at the same time -Performing Microdermabrasion first promotes the transdermal delivery rate -Reproducibility of dose delivered -Non-invasive -No trauma from injections

33. Copyright 2008 © Mattioli Engineering All rights reserved -Transderm fits perfectly in already existing protocols to improve and shorten outcome (compatibility). -Transderm allows users to have so many different applications in only one device. (substances delivered) -Transderm cancel completely the fear of needles and other invasive treatments. (Needles free injection system) -Transderm is the Top N.1 technology FDA cleared as “alternative to injections”. Advantages of Dermoelectroporation®

34. Copyright 2008 © Mattioli Engineering All rights reserved (source Aesthetic Buyers Guide 2006 ) The Growth of non surgical procedures. (source Aesthetic Buyers Guide 2006 ) “Growth of non-surgical aesthetic procedures is outpacing surgical procedures by a margin of three to one, with dermal fillers being only second to Botox in this category. This demonstrates that the consumer shift towards less invasive correction and heavily towards the non invasive segment.” “The global dermal fillers market was valued at $442 million in 2005 – an increase of 25% from the previous year.” Advantages of Dermoelectroporation®

35. Copyright 2008 © Mattioli Engineering All rights reserved BODY SHAPING MARKET Aesthetic Buyers Guide 2006 – “The global market for body shaping devices continues to expand strongly. Over the next five years, overall sales of body shaping systems will rise 25.1% per year, from $182.8 million in 2005 to an estimated $559.9 million in 2010.” “In 2005, almost 69% of procedure fees were represented by liposuction, a surgical technique that offers virtually guaranteed removal of small fat deposits in a single procedure. However, risks associated with surgery and relatively long recovery times will result in minimal procedure growth of just 3.5% per year for liposuction, while newer, non-invasive therapies will expand rapidly.” Advantages of Dermoelectroporation®

36. Copyright 2008 © Mattioli Engineering All rights reserved Benefits of Dermoelectroporation® Some of the Benefits Dermoelectroporation® can give: 1) Patients are not more afraid of any “was-invasive” procedure 2) No psychological shock in getting the treatment done 3) No risk of contamination hazard due to needles 4) Increasing number of treatments per day/month because…

37. Copyright 2008 © Mattioli Engineering All rights reserved Benefits of Dermoelectroporation® Transderm Increases the number of happy patient’s!..word of mouth!!

38. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Dermoelectroporation®:Results

39. Copyright 2008 © Mattioli Engineering All rights reserved Courtesy of Dr. Jaggy Rao, MD University of Edmonton,Alberta,Canada Before Rhythids - Canada After 2 sessions – 2 weeks apart each other 3ml Hyaluronic acid 15mg/ml

40. Copyright 2008 © Mattioli Engineering All rights reserved Stratum Corneum EpidermisDermisHypodermis 1.700.000dalton Hyaluronic acid delivery through the dermis to hypodermis using Transderm® ionto system Courtesy of Dr. Jaggy Rao, MD University of Edmonton,Alberta,Canada Biopsy on HA - Canada

41. Copyright 2008 © Mattioli Engineering All rights reserved Cellulite treatment - Italy Mattioli Engineering © All rights reserved – Do not distribute – For internal use only FOR EDUCTIONAL PURPOSES ONLY After Before Hairdresser, 44 years old Courtesy of Prof. Massirone, President A.M.E, A.M.I.Est. -. Milan Italy 11 patients - Females. 11 patients - Females. II, III and IV level cellulite. II, III and IV level cellulite. 8 consecutive weeks, once per week session. 8 consecutive weeks, once per week session. 1 ml Aminophylline + 2 ml Lymdiaral + 2 ml Veno-N. 1 ml Aminophylline + 2 ml Lymdiaral + 2 ml Veno-N.

42. Copyright 2008 © Mattioli Engineering All rights reserved Cellulite treatment - Italy Mattioli Engineering © All rights reserved – Do not distribute – For internal use only FOR EDUCTIONAL PURPOSES ONLY AfterBefore Shopkeeper, 34 years old Courtesy of Prof. Massirone, President A.M.E, A.M.I.Est. -. Milan Italy 11 patients - Females. 11 patients - Females. II, III and IV level cellulite. II, III and IV level cellulite. 8 consecutive weeks, once per week session. 8 consecutive weeks, once per week session. 1 ml Aminophylline + 2 ml Lymdiaral + 2 ml Veno-N. 1 ml Aminophylline + 2 ml Lymdiaral + 2 ml Veno-N.

43. Copyright 2008 © Mattioli Engineering All rights reserved Cellulite & Adiposity Treatment -USA FOR EDUCTIONAL PURPOSES ONLY befor e after Cellulite Treatment Protocol: Delivered every 1-2 weeks until desired result is achieved (usually 3-8 treatments) Areas are referred to as abdomen, thighs, etc. Per 5 cc syringe:4 cc Hyaluronidase 300 units/mL+ 4 cc L-carnitine 500 mg/mL+ 2 cc Phosphatidylcholine 100 mg/mL 4 syringes used per session. Courtesy of Dr. suneil Jain -. Scottsdale AZ - USA

44. Copyright 2008 © Mattioli Engineering All rights reserved Post-liposuction correction for abnormal fat deposition-USA FOR EDUCTIONAL PURPOSES ONLY befor e after Courtesy of Dr. suneil Jain -. Scottsdale AZ - USA Body Sculpting Protocol: Delivered every 1-2 weeks until desired result is achieved (usually 2-10 treatment) Areas are referred to as abdomen, lateral thigh, medial thigh & back. Per 5 cc syringe: 2 cc L-carnitine 500 mg/mL + 3 cc Phosphatidylcholine 100 mg/mL 4 syringes used per session.

45. Copyright 2008 © Mattioli Engineering All rights reserved Courtesy of Dr. Chuah, MD Kuala Lumpur - Malaysia Lifting - Malaysia Delivered once for total of 1 treatment. 5cc Super PLD Prepare solution using a 5cc syringe filled by Hyaluronic Acid cocktails through Super PLD. Ultrapeel microdermabrasion Ultrapeel microdermabrasion - arm test, 2 passes mid lvl power -followed by hand gommage. 10mins Transderm® Deliver transdermally HA cocktail 10mins each side medium time using Transderm® technology. Mask Apply Calmin Mask for 10 minutes Basic SPF Apply Basic cream and SPF cream

46. Copyright 2008 © Mattioli Engineering All rights reserved Stratum Corneum Epidermis Dermis Hypodermis 800.000dalton Hyaluronic acid delivery through the dermis to hypodermis using Transderm® ionto system Biopsy with Hyaluronic acid Courtesy of Dr. Stefania Pacini, MD University of Florence,Italy

47. Copyright 2008 © Mattioli Engineering All rights reserved Test of minor on an untreated part FOR EDUCTIONAL PURPOSES ONLY Botulinum toxine for HyperHydrosis Courtesy of Dr. M.Cavallini, Plastic surgery specialist, Milan, Italy Before After 6 cases – all female patients 6 cases – all female patients Sweating measurement with Test of minor Sweating measurement with Test of minor Delivery of 50 units of botulinum toxine per axilla (diluted with 2ml saline solution) Delivery of 50 units of botulinum toxine per axilla (diluted with 2ml saline solution) Time of treatment: 10 minutes Time of treatment: 10 minutes Control after 2 weeks Control after 2 weeks Test of minor to quantify the result after 14 – 20 days. Test of minor to quantify the result after 14 – 20 days.

48. Copyright 2008 © Mattioli Engineering All rights reserved –Botulinum Toxin magnification 150.000dalton Botulinum Toxin transdermal delivery till muscles using Transderm® ionto system Courtesy of Dr. Stefania Pacini, MD University of Florence, Italy Biopsy with Botulinum toxine Stratum Corneum EpidermisDermis Deep Hypodermis Muscles Scientific complete doocumentation available from April 2007

49. Copyright 2008 © Mattioli Engineering All rights reserved Mattioli Engineering’s Solution Mattioli Engineering’s Solution Dermoelectroporation®:Summarizing……

50. Copyright 2008 © Mattioli Engineering All rights reserved In other words…. Dermoelectroporation  technology …… –utilizes –utilizes the skin’s water based “channels” –Increasepermeability macro-molecules –Increase the skin permeability to allow transdermal delivery of micro-molecules and macro-molecules –Controlledpulses (Average current value on the patient is zero). –Controlled electrical pulses delivery (Average current value on the patient is zero). –No modificationpHno electrolysis –No modification of the ionic drug solutions pH and no electrolysis effect of the ionic solution itself. is faster –Dermoelectroporation  is faster than traditional Ionthophoresis devices to deliver the same amount of ionic drug solution. does not need –Dermoelectroporation  does not need any skin pH- Compensating patch, nor pre-charged compounds, nor carrying Gel nor others media to get the drug successfully delivered.

51. Copyright 2008 © Mattioli Engineering All rights reserved Any Questions? Dermoelectroporation® provides..