I Skin Pen 2014 BELLUS MEDICAL LLC ALL

1. 2 History of Microneedling Important milestones in the development of microneedling ► First described by the founder of mesotherapy, Dr. Michel Pistor, who didn’t employ the method himself but came up with the concept that pricking skin would promote collagen formation. * *Pistor, M. Presse Med. 1958 Jun 4; 66(44): 999 -1000 2

1. 3 History of Microneedling Important milestones in the development of microneedling ► 1995: Subcision, a new method of subcuticular undermining for the ► Mechanism of action is two-fold: 1. Releasing actioncutaneous of the procedure treatment of depressed scars and wrinkles is 2. New connective tissue via the wound-healing introduced. * response *Orentreich DS, Orentreich N. Dermatol Surg. 1995; 21: 6543– 9 3

1. 4 History of Microneedling 1997: Needle dermabrasion using a “tattoo pistol” to treat scars. * ► Intended to remove the tension and tightness in the skin caused by scarring ► Patients receiving skin-colored tattoos over facial scars saw evidence of pigmentation after 1– 2 years even though the tattoo pigment was long gone ► Scars were immensely improved in texture, appearance and color ► Not feasible, due to time and laborintensive nature of using just one *Camirand A, Doucet J. Needle dermabrasion. Aesthet Plast Surg. 1997; 21: 48– 51. needle to treat scars 4

1. 5 History of Microneedling 1998: Dr. Des Fernandes of South Africa presented his findings on needling at a conference in San Francisco* ► Introduced needling device, a small needle stamp, to induce collagen and used as a regular treatment in his surgical practice. *Fernandes D. , Minimally invasive percutaneous collagen induction. Oral Maxillofac Surg Clin North Am. 2006; 17: 51– 63 5

1. 6 History of Microneedling 2000: Horst Liebl, inventor of the original German Dermaroller, designed the very first microneedling medical device ► Revolutionized a formerly time-consuming and labor-intensive technique ► Consisted of many fine needles on a drum-shaped roller device ► Ability to treat larger areas of the skin easily and quickly. 6

1. 7 History of Microneedling 2004: Clinical Resolution Laboratory, a California company, redesigned the device, called MTS Roller 7

1. 8 Introducing Skin. Pen II 2014: The next step in Microtherapy Skin. Pen II is a medical-grade, state-of-the-art precision tool available only through medical professionals. Skin. Pen II works by creating a series of hundreds of microscopic channels into the dermis to stimulate the skin’s natural production of new collagen and elastin, helping skin to look and feel healthier. Skin. Pen II is designed to address various dermatologic conditions, such as: ► Fine lines or ► Atrophic acne moderate wrinkles scars ► Diminished skin ► Stretch marks texture, tone and ► Traumatic scars color ► Photo aging 8

1. 9 Skin. Pen Modernizes Microneedling Skin. Pen provides the safety and efficiency expected by today’s busy medical practice: ► Versatility efficiency and • Cordless • Disposable needle tips • Adjustable needle depth • Suitable for Fitz I-VI • Treats small facial areas to large body surfaces • Powerful motor reaches endpoint faster ► Safety • Sterile needle tips • Bio-Sleeve • Bio-Sheath 9

Advanced Microneedle Cartridge Exhaust port prevents suction and reduces risk of broken capillaries Bio-Sleeve prevents fluids from leaking beyond the microneedle cartridge 12 medical-grade 32 -gauge needles minimize epidermal destruction 10

Additional Layer of Protection. Custom, disposable Skin. Pen Bio. Sheath, combined with the Advanced Microneedle Cartridge, virtually eliminates the risk of crosscontamination. 11

1. 15 Efficiency For dermal rollers, the number of microchannels increases as a function of the number of passes made. 1 pass 3 passes 5 passes 10 passes 15 passes *Figure from: The AAPS Journal, Vol. 13, No. 3, September 2011 12

1. 16 Efficiency For Skin. Pen, the number of microchannels depends on how quickly you move the Skin. Pen across the surface of the skin. ► Needles cycle at 142 Hz or 142 “stamps”/second, potentially creating 1704 microchannels/second when moving the skin pen ► Slower movement at a rate of 1 cm/second, you can create roughly 4858 microchannels/ cm 2 of skin* ► Faster movement at a rate of 3 cm/second, you can create roughly 1621 microchannels/ cm 2 of skin* *Needles are ~1 mm apart (1000 microns) and the cartridge head has a diameter of 3. 5 mm ► The Skin. Pen produces significantly more microchannels with one pass than 13

1. 15 How Does Medical Needling Work? • 0. 5 mm – 3. 0 mm • Uses very fine, surgical stainless steel needles to create microscopic channels into the epidermis and dermis to release growth factors • Promotes scarless healing and deposition of normal woven collagen rather than scar collagen • Similar to Fraxel, without the negative loss of dermal papillae, potential destruction of melanocytes, abnormal collagen, coagulated growth factors • Allows 80% more product into the skin (compared to 7 -10% normally) 14

1. 10 Collagen Induction Therapy Microinjuries allow for release of serum containing cytokines and growth factors* *Fernandes, D. Oral. L Maxillofacial Surg Clin 2005; 17: 51 -63 15

1. 19 Phases of Wound Repair 16

1. 1 1 Collagen: Young vs. Old What does young vs. old skin look like? Biopsy of young skin showing thick bundles of collagen bundles. *Abd El-Aal NH, et al. J Dermatol 2012; 57: 181 -6 Biopsy of aged skin showing thin and loose collagen fibers (Masson- Trichrome × 100). 17

1. 1 1 Thickness: Young vs. Old Skin What does young vs. old skin look like? * Young skin showing normal epidermis and dermis with mean epidermal measurement of 37. 4±µm. *Abd El-Aal NH, et al. J Dermatol 2012; 57: 181 -6 Ages skin showing thinning of the epidermis and flattening of the dermal epidermal junction (DEJ) with the mean epidermal measurement of 17. 6± 8µm. 18

1. 12 Collagen Induction Therapy CIT Promotes deposition of fresh new collagen without scar formation* Left, before CIT. Right, six months after CIT, more collagen (pink) and elastin (brown) can be detected. Estimated > 400% more collagen and improved epidermal/dermal thickness *Fernandes, D. Oral. LMaxillofacial Surg Clin 2005; 17: 51 -63 19

1. 13 Increased Dermal Thickness Before Afte r Patient had an increase in dermal thickness after 5 months. Dermal thickness increased from 1. 91 mm to 2. 41 mm. Moon, HS et. al; Department of Dermatology, Eulji University School of Medicine 20

Creation of microchannels in the skin with minimal damage to epidermis* ► Minimal damage to tissue equals 21

Skin. Pen Advantage Microneedling offers a simple and safe modality to improve the appearance of acne scars without risk of dyspigmentation in patients of all skin types. ► 60 patients of skin types phototype I to VI were treated with microneedling for treatment of acne scars • Three treatments at monthly intervals. • Evaluated by using a Global. Aesthetic Improvement Scale (GAIS), and analyzed statistically by computerized image analysis of the patients’ photographs. Fabbrocini G, et al. . J Dermatolog Treat. 2012 Dec 8. [Epub • Average reduction of 31% of scarring. ahead of print]. • No short- or long-term dyschromia was observed. 22

1. 17 Microchannel Characteristics Recovery of skin barrier function following microneedling treatment as measured by transepidermal water loss (TEWL) Figure from: The AAPS Journal, Vol. 13, No. 3, September 2011 23

1. 18 Microchannel Characteristics INTACT N SKI 0 HOUR S 4 HOUR S 6 HOUR S 8 HOUR S 10 S HOUR 12 S 18 S 24 S HOUR Figure from: The AAPS Journal, Vol. 13, No. 3, September 2011 Calcein imaging to study closure of microchannels formed by 0. 7 mm microneedles. Channels closed by 18 hours post treatment, showing the reversible nature of the channels. 24

1. 20 Comparison with Other Treatments 25

1. 21 Lasers vs. CIT Advantages of CIT over laser treatments ► The biggest differences are cost and treatment recovery time. ► Either will take several sessions to treat your acne scars. ► Lasers run risk of post-inflammatory hyperpigmentation; CIT does not. ► The recovery time is longer between laser treatments than it is with CIT. ► Microneedling helps your body to create more collagen naturally. ► CIT is does not burn your skin. ► CIT tightens what is already there. 26

1. 22 Comparison with IPL Collagen Induction Therapy in 54 mice (IPL vs. microneedling) ► 18 control mice ► 18 IPL mice ► 18 microneedling mice Moon, HS et. al; Department of Dermatology, Eulji University School of Medicine 27

1. 23 Comparison with IPL Skin Thickness Moon, HS et. al; Department of Dermatology, Eulji University School of Medicine 28

1. 24 Comparison with IPL Histology (MT stain x 100) Control IPL Microneedling Moon, HS et. al; Department of Dermatology, Eulji University School of Medicine 29

1. 26 Comparison with IPL Collagen Quantitation (Western Blot) ► β-actin serves as a “loading control” to show the same amount of sample was loaded for each experimental group ► As can be seen here, the Western Blot confirms the elisa assay results showing significantly more production of collagen protein in the micro 3 -C 3 -I 3 -M 4 -C 4 -I 4 -M needling group Collagen of mice (3 -M and 4 -M) as opposed to the ß-actin control (C) or IPL (I) Moon, HS et. al; Department of Dermatology, Eulji University School of Medicine 30

1. 27 Comparison with IPL Conclusion: 2. Skin thickness: Control < IPL < Microneedling • MT Stain (collagen fiber): Control < IPL < Microneedling • Collagen quantative anaysis (ELISA, WB): Control < IPL < Microneedling 31

Questions? 32

Befor e After five treatments Photos courtesy of Dr. Christie Matter, North Texas Dermatology. 33

Befor e After four treatments Photos courtesy of Cathy Presnick, A Perfect Complexion LLC 34

Befor e After five treatments Photos courtesy of Cathy Presnick, A Perfect Complexion LLC 35

Befor e After one treatment Photos courtesy of Spectacular Skin 36

Before After one treatment First pass at 0. 5 mm; second pass at 1. 0 mm. Photos courtesy of Dr. Ken Oleszek, La. Fontaine Aesthetics 37

Before After one treatment First pass at 0. 5 mm; second pass at 1. 0 mm. Photos courtesy of Dr. Ken Oleszek, La. Fontaine Aesthetics 38

Before After one treatment Six weeks after one treatment Photos courtesy of Dr. Christie Matter, North Texas Dermatology 39

Befor e After two treatments Photos courtesy of Spectacular Skin 40

Befor e After three treatments Photos courtesy of Christy Bunyan, Licensed Aesthetician, North Texas Dermatology 41

Befor e After one treatment Photos courtesy of Spectacular Skin 42

Positioning Skin. Pen in your practice • Stand alone treatment or in combination with other treatment modalities • Patients at high risk of post-inflammatory hyperpigmentation • Patients with no time for downtime • Patients who desire a more “natural” or approach to skin rejuvenation • A cost effective alternative to laser therapy • To rebuild epidermal health in ablative therapy patients 43

Partnering with Bellus Medical ► On-site training and certification ► Proven implementation strategy: Skin. Pen Bootcamp ► Advanced education ► Customer-centric website: skinpen. com ► Digital marketing and social media ► Skin. Pen. com physician finder ► Premier Partner program 44

Skin. Pen Boot Camp Designed to: ► Introduce your patients to Skin. Pen ► Train your staff to educate patients, optimize results, and sell packages ► Teach your practice how to turn satisfied patients into practice advocates to increase patient referrals ► Generate revenue. We’ll help you pay for your Skin. Pen in one day! 45

Social Media Bellus Medical provides a digital marketing team dedicated to promoting your practice. Skin. Pen: ► “Likes” you on Facebook ► “Follows” you on Twitter ► “Adds you to our circle” on Google+ ► “Follows” you on Pinterest ► “Shares” your You. Tube videos 46

Premier Partner Program ► Preferred placement on skinpen. com Physician Finder ► Lifetime warranty of Skin. Pen device ► Upgrade Skin. Pen device to the next generation at no charge ► $1000 off on additional devices ► 25% discount on marketing materials ► Preferred pricing on Advanced Training Courses 47

The Revenue Skin. Pen can add profitability to your practice while offering a cost-effective and efficacious treatment to your client ► Packaging options ► Pay for your Skin. Pen in one day during Skin. Pen Bootcamp. Example: 5 patients purchase a package of 3 “training” package for $700 each = $3, 500 ► Earn $140, 000 annually for your practice with just three new patients per week at $300/treatment Each patient represents $900 revenue (3 procedures x $300) 48

Questions? 49

Operating Your Skin. Pen II 50

Using Skin. Pen Bio-Sheaths 51

Operating Your Skin. Pen Installing the Microneedle Cartridge Turn the dial to zero. Install the microneedle cartridge by pressing down and rotating clockwise until the cartridge will turn no further. To remove, turn dial to zero, then rotate cartridge counterclockwise until it releases. 52

Operating Your Skin. Pen Adjusting Needle Depth The needle depth ranges from 0. 0 to 2. 0 mm by turning the needle dial clockwise (deeper) or counterclockwise (shallower). The arrow points to the current depth. 53

Operating Your Skin. Pen Chargin g 1. Screw the battery unit into the charging unit. 54

Operating Your Skin. Pen Chargin g 2. Insert the charger adapter into the charging unit and insert the plug into a power outlet. The red light on the charging unit will come on. Charge until the light turns green (approximately 3 hours). 55

Operating Your Skin. Pen Chargin g 3. After charging, unscrew the battery and screw in the Skin. Pen II. 56

Operating Your Skin. Pen Changing Speed Skin. Pen II provides three speed selections. The pen will start on the speed on which it was previously powered off. Most often, you will operate the pen at the highest speed. Press on/off button one time to move through each of the three speed settings. The flash speed of the indicator light will change accordingly as you move from slow, medium, and high speeds. 57

Questions? 58

Skin. Pen II Instructions for Use ► Overview Skin. Pen is a microneedling technology designed for use by skincare professionals. Sterile Microneedle cartridges are provided sterile for single use. ► Intended Use Skin. Pen II is an FDA Registered Class I Medical Device intended for the treatment of the symptoms of aging skin and scars, including acne, surgical and trauma. 59

Contraindications Skin. Pen is contraindicated for patients with: ►A history of keloid scars, scleroderma, collagen vascular diseases or cardiac abnormalities ►A hemorrhagic disorder or hemostatic dysfunction ► An active bacterial or fungal infection 60

Precautions and Warnings Skin. Pen has not been evaluated in the following patient populations, and as such, precautions should be taken when determining whether to treat: ► Scars and stretch marks less than one year old ► Women ► Keloid who are pregnant or nursing scars ► Patients with history of eczema, psoriasis and other chronic conditions ► Patients with history of actinic (solar) keratosis ► Patients with history of herpes simplex infections ► Diabetics ► Patients ► Skin or patients with wound-healing deficiencies on immunosuppressive therapy with presence of raised moles or warts on targeted area 61

Pre-treatment Considerations ► Avoid sun exposure/burns 24 hours prior to treatment. ► Discontinue use of retinoids 12 hours prior to treatment. ► Avoid treatment on patients with active breakouts or open lesions. ► Allow at least 12 hours after autoimmune therapies before using Skin. Pen II. ► Wait six months following isotretinoin use. ► Fitz IV-VI, pigment may darken prior to lightening. 62

Treatment Instructions 1. Have patient complete consent form. 2. Explain the Skin. Pen II procedure to the patient and set expectations. 3. Cleanse patient’s face with a gentle cleanser to effectively remove makeup, sunscreen and surface oils. 4. Take “before” pictures of the treatment area. • Apply numbing cream to the patient’s face and leave on for 15– 50 minutes, based on product instructions. • Remove numbing cream and thoroughly cleanse again with a gentle cleanser. continued on next slide 63

Treatment Instructions continued 7. Wipe Skin with alcohol to ensure all numbing agent is removed. Important: Anything remaining on the skin or placed on the skin pre-procedure may increase complications post procedure. At this time, Bellus Medical only recommends use of Hydra. Max Replenishing Serum. 8. Apply a disposable Bio-Sheath to Skin. Pen II to ensure no blood or fluid comes in contact with the pen. 9. Install the Advanced Microneedle Cartridge based on the instructions provided under “Installing the Microneedle Cartridge. ” continued on next slide 64

Treatment Instructions continued 10. Apply a thin layer of Hydra. Max Replenishing Serum or sterile saline to assist the glide of Skin. Pen II. If the layer is too thick or if the numbing agent was not adequately removed from the skin, the microneedle cartridge may become clogged. 11. Start at a depth setting of 0. 25 mm. If you do not see even erythema (redness), gradually increase the depth to a maximum of 1. 0 mm on the face or 2. 0 mm on the body. Lower to 0. 25 mm to perform treatment on the forehead or around the orbital rim. continued on next slide 65

Treatment Instructions continued 12. Divide the face into four quadrants. Start with the right cheek, move to chin/lip/nose, and finish with forehead. 13. As you work each area, hold the skin taut and glide the pen in controlled horizontal motions. Repeat with vertical motions in the same area. Repeat the pattern if the erythema endpoint has not been reached. Depth may be increased within the guidelines if necessary. You may use gentle, one-directional circular motions in small targeted area if needed. 66

Proper Technique for Skin. Pen II 1. As you work each area, hold the skin taut and glide the pen in controlled horizontal motions. 2. Repeat with similar controlled vertical motions in the same area. 3. Repeat the pattern if the erythema endpoint is not reached. Depth may be increased within guidelines if necessary. • May use gentle, 67

3. 5 Recommended Needle Depth Average Skin Thickness Measurements Site AVG ABC Upper lip Lower lip Philtrum Chin Upper eyelid Lower eyelid Forehead Right cheek Site 0. 83 ± 0. 17 0. 82 ± 0. 15 0. 83 ± 0. 10 1. 15 ± 0. 11 0. 38 ± 0. 09 0. 82 ± 0. 21 1. 03 ± 0. 15 Left cheek Malar eminence Submental Nasal tip Nasal dorsum Right neck Left neck AVG ABC 1. 17 ± 0. 08 1. 05 ± 0. 45 0. 89 ± 0. 19 1. 22 ± 0. 15 1. 15 ± 0. 11 0. 52 ± 0. 23 0. 54 ± 0. 20 1. 07 ± 0. 09 Plast Reconstr Surg. 2005 May; 115(6): 1769 -73 68

Post-Treatment Instructions Immediately 1. Gently use sterile gauze dampened with sterile saline to pat down the treated area. • Reapply a thin layer of Hydra. Max Replenishing Serum. IMPORTANT: Some of the microchannels created may remain open up to 4 hours. Caution should be exercised when placing additional products on the skin during this time. Unexpected complications may occur when products not proven safe for use with microneedling are applied post-procedure. • Review after-care instructions with patient. • Schedule next appointment at 4 weeks. 69

Post-Treatment Instructions Days 2 and 3 1. Cleanse: Use a gentle cleanser. 2. Restore: Apply Hydra. Max Replenishing Serum over entire treatment area to reduce inflammation and hydrate the skin. • Protect: Apply antioxidant SPF 30 sunscreen of your choice. Day 4 Resume normal skin care routine. 70

Post-Treatment Expectations ► Day 1: Patients should expect mild to moderate edema and erythema, similar to a mild sunburn. There may be some mild bruising in some patients as well. ► Day 2: Some persisting redness may be present, but all redness bruising and swelling should be diminishing. ► Day 3: Most redness, bruising and swelling should be nearly gone. Normal appearance with makeup may be achieved. ► Day 4: Patient should appear mostly normal at this point with some minor swelling. 71

Possible Side Effects Side effects are rare with microneedling, especially when using disposable needles. However, some possible rare side effects may be: ► Allergic reaction to steel or serums used ► Robust inflammation of treated area ► Persisting itching ► Cutaneous eruption ► Reactivation of pre-existing HSV If any of the above effects or any other effects of concern are noted after treatment, make sure the supervising physician is notified immediately to avoid further 72 complication.

Treatment Protocols ► Series of 1– 3 Tx at 4 -week intervals • Large pore • Texture size • Uneven skin • Fine lines tone ► Series of 3– 6+ Tx at 4 -week intervals • Moderate to deep • Atrophic acne wrinkles scars • Striae/stretch marks • Traumatic scars 73

Combination with Other Therapies ► Neurotoxins. It is recommended that needling not be performed within 48 hours of injection with any toxin, as increased perfusion and edema may diminish the effect and distribution of the toxin. ► Fillers. Medical discretion should be used in determining when needling is performed following injection of dermal fillers, as performing needling too soon may possibly lead to adverse inflammatory reactions. Additionally, care should be taken when treating over fillers known to produce an inflammatory response (e. g. , foreign body granuloma) following trauma to 74 the tissues adjacent to the filler.

Questions? 75

Thank You! 76