Lecture by Dr. Patrick J. Treacy to Las Vegas Cosmetic Conference 2011 about his experiences and preferences with different European Botox and Dermal Fillers

1. Experience with European BotoxAnd Dermal Fillers Where my preferences stand June 25th, 2011

2. BOTULINUM TOXIN European Brands Azzalure ® Bocature® Botox® Dysport® Neurobloc® Vistabel® Xeomin®

3. Azzalure ®

4. Azzalure ® Azzalure ® Azzalure®, botulinum toxin type A, has been available in the U.K. and Ireland since the early 1990s as the brand name Dysport®, which has licences for various indications in 67 countries worldwide, including the United Kingdom and many European markets. It gained approval for cosmetic use in the UK in early 2009 and is marketed for this indication, with dosing specific to treat glabellar (frown) lines, under the brand name Azzalure®. It is manufactured by the French company Ipsen and commercialised by Galderma.

5. BOCOUTURE ®

6. Bocouture ® BOCOUTURE®, botulinum toxin type A, has been available in the U.K. and Ireland since 2008 as the brand name Xeomin ®, which is licenced in Europe for blepharospasm and cervical dystonia. It gained approval for cosmetic use in the UK in July 2010 and is marketed for this indication, with dosing specific to treat glabellar (frown) lines, under the brand name Bocouture®. Bocouture® claims to be an innovative Botulinum type A formulation, in which the complexing proteins have been removed by an extensive purification process from the botulinum toxin complex.

7. Bocouture ® It is widely accepted that the bacterial protein present in other products play a role as promoters of an immune reaction, resulting in a loss of effect and reduction in duration of activity. Studies show that Bocouture®, without the complexing proteins, has the lowest content of protein of all of the available botulinum toxins and furthermore show that repeated application of Bocouture®, even in high doses, does not induce the formation of neutralising anti-bodies. This means that Bocouture® is able to provide similar results to those achievable with the other products without the risk of antibody formation, providing continual long lasting effects. This could be relevant when large doses are being used for medical indications, but many industry experts questions the relevance when this product is used for cosmetic purposes.

8. BOTOX ®

9. Botox ® Currently the number one non-surgical aesthetic treatment in the U.S., Botox® is also the leading brand of botulinum toxin type - A in terms of documented clinical trials and practical use around the world. Botox® was the first botulinum toxin to gain a cosmetic licence endorsing its use for glabellar lines and wrinkles. It is approved for this indication in the U.S. and around twelve other countries in the world, and was licenced for this use in the U.K. in March 2006 under the brand name Vistabel ®

10. Dysport ®

11. Dysport ® Dysport ® Dysport®, botulinum toxin type A, has been available in the U.K. since the early 1990`s and has licences in 67 countries worldwide including the United Kingdom and many European markets. It is manufactured by the French company Ipsen. The product is licensed for cosmetic use in a number of markets e.g. glabellar (frown) lines in Germany. It also gained approval for cosmetic use in the UK in early 2009 and is marketed for this indication, with a dosing specific to treat glabellar lines, under the brand name Azzalure ® by Galderma. .

12. Neurobloc ®

13. Neurobloc ® Neurobloc ® Neurobloc® became available in the U.K. in 2001. There is limited experience in the use of this type of toxin, and the product does not currently have approval for cosmetic use anywhere in the world. As a result of this very few U.K. practitioners have any experience in the use of this product for lines and wrinkles. Generic name Clostridium botulinum type - B neurotoxin complex

14. Neurobloc ® Myobloc® (rimabotulinumtoxinB) Injection is soldin the US and approved in Canada. MYOBLOC is also being distributed as NeuroBloc® (Botulinum Toxin Type B) in the EU, Norway and Iceland and as Myobloc®(Botulinum Toxin Type B) Injectable Solution in Korea.

15. VISTABEL ®

16. Vistabel ® Vistabel ® Botox ® was the first botulinum toxin to gain a cosmetic licence endorsing its use for glabellar lines and wrinkles. It was licenced for this use in the U.K. in March 2006. It gained approval for cosmetic use in France in early 2003 and is marketed there under the brand name Vistabel®. With dosing specific to treat glabellar lines, it is also marketed for cosmetic use in the UK under the brand name Vistabel® and is the first brand of botulinum toxin type A licensed for cosmetic use in the UK.

17. Xeomin ®

18. Xeomin ® Launched in the UK and Ireland in 2008, Xeomin® is the third botulinum toxin type A to be promoted in the UK. Xeomin® claims to be an innovative Botulinum type A formulation, in which the complexing proteins have been removed by an extensive purification process from the botulinum toxin complex. In contrast to the other commercially available preparations, Xeomin® contains the pure 150 kD neurotoxin.

19. Xeomin ® Studies show that Xeomin®, without the complexing proteins, has the lowest content of protein of all of the available botulinum toxins and furthermore show that repeated application of Xeomin®, even in high doses, does not induce the formation of neutralising anti-bodies. This means that Xeomin® is able to provide similar results to those achievable with the other products without the risk of antibody formation, providing continual long lasting effects. This could be relevant when large doses are being used for medical indications, but many industry experts questions the relevance when this product is used for cosmetic purposes.

20. MY PREFERENCE DYSPORT ®

21. DERMAL FILLERS European Brands AQUAMID ® ARTECOL ® ATLEAN ® BELOTERO ® Bio ALCAMID ® CRISTAL ® CRM ®

22. DERMAL FILLERS European Brands ELLANSE ® EMERVEL ® EVOLENCE ® JUVADERM ® MATRIDUR ® MATRIDEX ® NOVABEL ®

23. DERMAL FILLERS European Brands PREVELLE ® PURAGEN ® RADIESSE ® RESTYLANE ® REVANESSE ® REVIDERM ® SUCCEEV ®

24. DERMAL FILLERS European Brands TEOSYL ® VARIODEM ® ZYDERM ® ZYPLAST ®

25. Aquamid ®

26. Aquamid ® Aquamid™ This product was launched in the U.K. in 2003. Aquamid™ contains about 2 - 3% of cross-linked polyacrylamide gel network and with the remaining part of 97 - 98% being water. The molecule is not dissolved in water, but "swollen" like a sponge. The gel is in dynamic equilibrium with the surrounding tissue, but still the polymer retains its ability to hold water and remains elastic over an extended time.

27. Aquamid ® Aquamid™ has been used for aesthetic correction for more than ten years in 30,000 patients in the previous Soviet Union and Europe. Polyacrylamides have been used for many years in the United States and Europe for treatment of drinking water, and is also found in soft contact lenses, and tissue implant material.

28. MY PREFERENCE DYSPORT ®

29. Atlean ® Atlèan™ ßTCP French company ABR Development (now part of Stiefel Laboratories Inc.), the pharmacists who invented Sculptra ® launched their new volumising filler product, Atlèan™ βTCP, in the UK and Ireland in June 2007. As a result, you may only come across a few practitioners using this product currently.

30. Atlean ® Atlèan™ is a tri-calcium phosphate product in the form of a white gel which the manufacturer claims gives the same volumising and sculpting visual effects as the poly-l-lactic acid based filler, Sculptra™ but without the 4 - 6 week wait to see the benefits. This is due to the fact that Atlèan™ also contains hyaluronic acid which gives an immediate visible result, which lasts for up to 3 months, whilst the tri-calcium phosphate helps to stimulate the production of new collagen in the treated area for a longer lasting result. What does it contain? A 1ml syringe of Atlèan™ contains 70mg of Tri-Calcium Phosphate (TCP), 18mg of hyaluronic acid and 8mg of carmellose sodium (a stabilising agent), within a 1ml of buffered saline solution. TCP is bio-compatible (compatible with body tissues), bio-degradable, immunologically inert (i.e. does not effect the immune system) and non-toxic. It has been used in medicine for years, for example, in bone regeneration after fractures. The non-animal based hyaluronic acid is derived from bacterial fermentation.

31. Atlean ® The manufacturer claims that the product can help cause new collagen growth rather than just mechanically filling depressions, making it a sculpting agent rather than just a wrinkle filler; although the addition of a recognised wrinkle filling agent (hyaluronic acid) into the product means that patient satisfaction from an immediate visible result is greater. What does it contain? A 1ml syringe of Atlèan™ contains 70mg of Tri-Calcium Phosphate (TCP), 18mg of hyaluronic acid and 8mg of carmellose sodium (a stabilising agent), within a 1ml of buffered saline solution.

32. ELLANSE ®

33. Ellanse ® Ellanséis a new and unique non-animal, non-bacterial and non-human derived dermal filler family which are said by the manufacturer to be cost-effective by requiring less product, compared to others, for the same indications. The Ellansé family (S, M, L, E) has four distinctive duration formulations to choose from, from 1 to 4 years or more. Ellansé is composed of totally smooth polycaprolactone (PCL) microspheres (diameter of 25 – 50 μm) suspended in an aqueous carboxymethyl cellulose (CMC) gel–carrier and is constituted of 30% PCL microspheres suspended in 70% gel carrier.

34. EMERVEL® RANGE A complete range of products, with and without lidocaine, well differentiated for specific indications, to provide physicians the optimal choice to best meet patients needs Optimal gel textures thanks to a perfect balance : Science behind the concept

35. Key concept : Crosslinking ButaneDiol Diglycidyl Ether : well known crosslinker - Purification through dialysis Residual BDDE < 2ppm (FDA limit) HA (bacterial origin) modification by crosslinking Crosslinking Bind the polymers chains together Grafting Fix the BDDE to HA only from one side Does not modify the Texture (in red) Only the crosslinking could modify the texture of gel HA 35

36. Key concept : Crosslinking 1H NMR Determination of linker/HA ratio % mesured = % mono-linked + % di-linked

37. EVOLENCE ®

38. Evolence ® Launched in the UK at the beginning of 2005, EVOLENCE™ is a new, collagen-based dermal filler manufactured by ColBar LifeScience (now part of OrthoNeutrogena, a division of Ortho-McNeil Pharmaceutical, Inc., a Johnson & Johnson company). It was officially launched in Europe in October 2004 at the 13th EADV Congress in Florence, Italy. It is intended for the correction of wrinkles, nasolabial folds, scars, atrophy from disease or trauma, defects secondary to rhinoplasty (nose surgery), skin graft or other surgically-induced irregularities and other soft tissue defects or deficiencies.

39. Evolence ® What does it contain? The highly purified collagen in EVOLENCE™ is derived from porcine (pig) tendons. Due to their high degree of compatibility with the human body’s immune system, porcine collagen materials are often used in human medicine, e.g., in heart valve replacements, implantable lenses, and surgical wound dressings. How is it made? Using their patented Glymatrix™ technology, they firstly break down the source material into pure collagen molecules.

40. novabel ®

41. Novabel ® Novabel® is not a hyaluronic acid based injectable product but is in fact a patented, plant-based or alginate composition from sea algae which it is claimed results in an easier injection with much less swelling, making results more visible. An 18 month study has shown excellent safety results according to the company. Early indications are that results should persist for 12 months or more. The product will be available through trained UK cosmetic practitioners towards the spring and summer of 2010. Information will be updated at that time.

42. Novabel ® *** IMPORTANT ANNOUNCEMENT *** Sales and marketing of Novabel® temporarily suspended. Merz Aesthetics has suspended sales of its new flagship facial shaping product, Novabel®, amid concerns following reports of a few patients treated with the product in the infra-orbital region who suffered adverse reactions. In a letter out to its customers, Merz said; “Given the unique composition of Novabel an effective treatment has not yet been identified to quickly resolve these events. Reported: 30th June 2010

43. PREVELLE ®

44. Prevellle ® Having launched Puragen in late 2005, designed for the treatment of moderate to deep lines and wrinkles, Mentor Corporation went on to launch Prevelle™ in the UK in late 2007, a sister product aimed at fine lines and wrinkles around the mouth, eyes and forehead. Despite this joint portfolio Mentor is keen to highlight that the products are in fact distinct and technologically different, however they are meant to complement one another. Given the recent introduction, you may only come across a few practitioners using this product currently.

45. redexis ®

46. REVANSE ® Revanesse® and Redexis ® Revanesse® and Redexis® are two monophasic, non-animal hyaluronic acid based dermal filler brands manufactured in Canada by Prollenium and distributed in the UK by Boston Medical Group Ltd since 2010. Generic name Non-animal hyaluronic acid gel. Dextranomers(as found in the Redexis products) break down into sugars within 2 years.

47. succeev ®

48. Succeev ® Succeev® is a mono-phasic Hyaluronic Acid based dermal filler from Sanofi-Aventis Medical Aesthetics (the makers of Sculptra ®. It includes three formulations, ONE, TWO and THREE, for the correction of different types of wrinkles, from fine lines to deep wrinkles and lip augmentation. Succeev® One targets the superficial dermis to treat fine wrinkles Each pack contains 2 pre-filled syringes of 0.8ml of hyaluronic acid.

49. Teosyl ®

50. Teosyl ® Teosyal® The Teosyal® range, manufactured in Switzerland by Teoxane Laboratories and distributed in the UK by Lifestyle Aesthetics, consists of several monophasic hyaluronic acid based products of non-animal origin, which are highly biocompatible, offering patients immediate and long-lasting results. The Teosyal® range has a reduced protein and bacterial endotoxin level resulting in less hypersensitivity reactions. Teosyal® was launched in the UK in 2005.

51. VArioderm ®

52. Varioderm ® Varioderm™ The Varioderm™ range, manufactured in Germany by Adoderm GmbH and distributed in the UK by Medical Aesthetics Group, was launched in the UK in April 2008. As a result, you may only come across a few practitioners using this product currently. It consists of a range of very highly cross-linked, pure non-animal hyaluronic acid fillers available in 4 concentrations. Generic name Non-Animal Hyaluronic Acid (NaHA) gel.

53. Varioderm ® Varioderm™ The Varioderm™ range, manufactured in Germany by Adoderm GmbH and distributed in the UK by Medical Aesthetics Group, was launched in the UK in April 2008. As a result, you may only come across a few practitioners using this product currently. It consists of a range of very highly cross-linked, pure non-animal hyaluronic acid fillers available in 4 concentrations. Generic name Non-Animal Hyaluronic Acid (NaHA) gel

54. Evolence ® *** IMPORTANT ANNOUNCEMENT *** Johnson & Johnson announced their intention to discontinue the manufacture and marketing of EVOLENCE® products. Patients and medical professionals who may currently be using EVOLENCE® products can be assured that they remain effective for the approved indications with a favourable safety profile. EVOLENCE® products will continue to be supported for medical inquiries and adverse event reporting, in accordance with regulatory requirements. Reported: 3rd Nov 2009

55. THANK YOU FOR YOUR ATTENTION 55