Physician Reference Slides 2007. US Filler Market Evolution 2004 2006 FDA Approved December 2006 Wrinkles and Folds HIV Facial Lipoatrophy 1980’s Collagen.

Physician Reference Slides 2007

US Filler Market Evolution

2004 2006

FDA Approved December 2006

Wrinkles and Folds

HIV Facial Lipoatrophy

1980’s

Collagen Established Fillers 2-3 mos. durability (ZyplastTM, ZydermTM, etc.)

Approximate Timeline

Hyaluronic Acid Revolutionized Fillers 6 mos. durability (Restylane®, Juvederm®, Hylaform®, etc. )

Next GenerationLong-lasting: 12-18 mos. without being permanentMay last a year or more in many patients

2007

Radiesse received approval from the FDA December 26, 2006 for facial soft tissue augmentation– Treatment of facial wrinkles and folds, such as nasolabial

folds, marionette lines, etc.

– Correction of facial wasting as a result of HIV-associated Lipoatrophy

Radiesse is the first dermal filler to receive FDA approval for two facial aesthetic applications

US Regulatory Approvals

Radiesse is a safe, next generation cosmetic dermal filler aiming to become the new standard for long lasting correction of facial lines and

wrinkles. Clinical studies prove that in many patients Radiesse lasts a year or longer and delivers a natural look that results in very high patient

satisfaction.

Synthetic Calcium Hydroxylapatite (CaHA) microspheres [30%] suspended in a carboxy-methylcellulose resorbable aqueous gel carrier [70%]

Stimulates the body to produce new collagen

Pre-filled 1.3 cc & 0.3 cc syringes

No skin or allergy testing

No special handling requirements

Decalcified 25µm to 45 µm particles

Radiesse Not Only Fills, but Volumizes

When placed into soft tissue, Radiesse provides immediate correction

– Gel + CaHA Particles

Over time the gel is resorbed and the CaHA particles stimulate the body to produce collagen

– Collagen + CaHA Particles

Radiesse Stimulates NewCollagen Production

32 Weeks 78 Weeks

16 Weeks4 Weeks

Histology studies demonstrate increased collagen deposition around CaHA micro-spheres over a time course. Collagen fibers stain red using picrosirius red (60x mag).

6-Month Human Skin HistologyTissue infiltration (Light Blue Stain)

J. Cosmetic Laser Therapy 2004; 6: 223-226 by Ellen S Marmur MD, Robert Phelps MD and David J Goldberg MD, “Clinical, histologic and electron microscopic findings after injection of a calcium hydroxylapatite filler”

Radiesse Supports Natural Collagen Integration

CaHA particles are slowly dissolved into calcium and

phosphate ions through normal metabolic processes

CaHA particles post-implantation

Radiesse Particles Break Down Naturally

Dermal Filler(Immediate Correction)

Tissue Regeneration(Extended Correction)

Collagen

Hyaluronic Acid Poly-L-lactic Acid

Radiesse Provides Both Immediate Correction and Long Lasting Results

Radiesse is Safe- AE ProfileSimilar to Other Fillers

Hundreds of thousands of patients have been successfully injected with Radiesse worldwide

In the pivotal Nasolabial Fold clinical trial compared to collagen, Radiesse had fewer nodules and a similar safety profile

In another head-to-head clinical study comparing Radiesse to Restylane®, the adverse event profiles were similar for both products

**

* Urological applications used Radiesse’s sister product, Coaptite in clinical studies (75-125 microns)

Multiple Documented Studies Demonstrate the Efficacy and Safety of CaHA

™ ®

Radiesse is Safe- No Reported Granulomas

In two separate 100+ patient FDA Clinical Trials, Radiesse had zero granulomas

Radiesse is Safe- It will notForm Bone in Soft Tissue

Bone cannot be formed because:

– No osteo-progenitor cells or bone morphogenic proteins are present in the dermis

– The CaHA present in Radiesse is not bone- it is a mineral component found in bones and teeth

Radiesse stimulates the patient’s own collagen to be produced, resulting in a soft and natural appearance and feel

The CaHA microspheres are synthetically derived and break down naturally over time by the body’s own metabolic processes into Ca2+ and PO

3

2+ ions.

No ossification or calcification of CaHA has been reported in over 6 years of clinical use and >400,000 syringes injected

Radiesse is Safe- It will notObscure X-raysThe volume/density placed in facial injections will not interfere with x-rays

– If visible, it is only faint and whispy and will not interfere

– Barely visible on diagnostic x-ray

– Clearly evident bilaterally on CT scan, distinct from bone, and no masking of underlying structures

X-ray after 2.4 cc Radiesse injection in lower face CT Scan Immediately-post injection

6 Months 12 MonthsBaseline*

Continued safety follow-up & optionaltouch-up injection(Optional)

2 week*

(Optional)

4 week*

* Safety: 72 hour follow-up calls & 1-month safety visit after each injection

Canfield Scientific Core Lab

3 Blinded EvaluatorsInvestigationalSite

Prospective, randomized, controlled, split-face trial compared Radiesse to CosmoPlast®

Optimal Correction

3 Months

3 Months

FDA Nasolabial Fold Study

Live GAIS Rating at 6 MonthsAssessment by Treating Investigator

Radiesse

0% 20% 40% 60% 80% 100%

Worse

No Change

Improved

MuchImproved

Very MuchImproved

CosmoPlast

0% 20% 40% 60% 80% 100%

Worse

No Change

Improved

MuchImproved

Very MuchImproved

94.6% Improved

2.7% Improved

Volume vs. Cost Comparison

Average volume needed to reach Optimal Correction

(p<0.0001)

List price Estimated cost of Tx

Radiesse 1.2 cc $ 295 $ 295

CosmoPlast 2.4 cc $ 175 $ 411

Baseline Optimal 3 Month 6 Month

Rad

iess

e

Total Volume

1.5 mL

Co

smo

Pla

st

TotalVolume

3.6 mL

Representative Study Images

Adverse Event Analysis

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

Edem

a

Eryth

ema

Ecchy

mos

is

Other

Pain

Prurit

is

Needle

Jam

ming

Nodule

Allerg

ic Rea

ction

Embo

lizat

ion

Erosio

n

Extrus

ion

Granu

loma

Hemat

oma

Infe

ction

Necro

sis

Radiesse Control

Radiesse is safe

– The safety profile of Radiesse was comparable to the collagen control

Radiesse is effective

– Met all primary and secondary effectiveness endpoints

– >80% of Radiesse folds were improved at 3 and 6 months

– Radiesse found superior to collagen at 3 & 6 months

– Patients and Physicians preferred Radiesse (>96%)

NLF Study Conclusions

Facial Lipoatrophy Trial

Purpose–Safety and effectiveness of Radiesse

Sites–Stacey Silvers MD, New York (60 patients)

–Joseph Eviatar MD, New York (34 patients)

–Michael Echavez MD, San Francisco (6 patients)

Parallel Study with 30 patients in Canada by Dr. Alastair Carruthers

3 Months 6 Months 12 Months 18 Months 30 Months0 Months

Initial TreatmentPhase

Follow-up Phase

Baseline

4.7 cc 1.8 cc

Average Initial Volume6.5cc

2.4 cc

GAIS Results up to 18 Months

3 Monthsn=100

6 Monthsn=98

(before touch up)

12 Monthsn=98

(6mo after touch up)

Improved

Much Improved

Very Much Improved

No Change

Worse

2%

72%

26%

--

--

7%

86%

7%

16%

53%

31%

--

--

18 Monthsn=94

(12mo after touch up)

38%

44%

10%

9%

--

100% of Patients Improved through 12 Months

91% of Patients maintain

Improvement

No nodules or granulomas at large injection volumes

No product related serious adverse events in the study

Post-treatment expectations

– Pain on injection, resolves quickly

– Transient conditions resolving in a few days

• Redness

• Swelling

• Itching

• Bruising

Facial Lipoatrophy TrialSafety Summary

Baseline Month 6

Month 12 Month 18

40 yoMale

Total Volume8.0 mL

Representative Patient Photos

“Yes” at 3 months




Would you recommend Radiesse treatment? 99% 99% 99% 99%

Has the Radiesse treatment been beneficial to you? 100% 100% 100% 99%

Do you feel more attractive since receiving the Radiesse treatment? 98% 98% 98% 98%

Is your emotional wellbeing better since receiving Radiesse treatment?

91% 96% 97% 95%

Do you have more confidence in your appearance since receiving the Radiesse treatment?

98% 98% 99% 99%

Patient Satisfaction Through18 Months

Radiesse HIV StudyConclusions

Radiesse is safe

– No reports of serious adverse events

– Minor AE’s resolved within 7 days

Radiesse is effective

– 100% of patients were improved through 12 months

– > 90% of patients were improved through 18 months

– All primary and secondary endpoints were met

– > 90% patient satisfaction through 18 months

Facial Beauty

Facial Aging

Placement of Radiesse into the Skin

Objective is to fill the depression and structurally support the line and provide volume

– Inject Radiesse into the deep dermis and subdermal plane

– Use non-dominant index finger to guide needle

– Deeper threads can be placed to bolster depression

– Use thumb and forefinger to massage and mold Radiesse

Mark areas to be treated (if necessary) with patient in upright position

Make the patient comfortable by providing some level of anesthesia

27-gauge needle

1.25”, 1.5” or 0.5” needle can be used (area dependent)

Inject small amounts (0.05 cc) in multiple passes

Limit puncture sites and stop injecting prior to withdraw of the needle

Massage and mold area for desired look

Progressively bring the patient to full correction -no overcorrection necessary

Pearls of Wisdom for Injecting Radiesse

Nasolabial Folds with RadiesseLinear Threading and Fanning

Using 1.25” or 1.5” Needle Using 0.5” Needle



Susan Weinkle, MDTampa, FL

Before Immediately After(1.3 cc total)

Nasolabial Folds with Radiesse

Before Immediately After(1.3 cc total)


Henri Gaboriau, MD Seattle, WA

6 Months(No Touch-up)

Steven Bloch, MDHighland Park, IL

Before

12 months1.3 cc


Miles Graivier, MD Roswell, GA.

Pre Injection

1.4 cc

22 Months

0.6 cc touch up

24 Months 36 Months


Marionette Lines with RadiesseLinear Threading and Fanning

Use 0.5” or 1.25” 27g needle

Lidocaine infiltration may be suitable

Use fanning technique with retrograde threading to lift and fill marionette line

Be conservative with volume and do not place material too deep

Treat the entire zone- may include lateral chin area, not just the line

Progressively bring to full correction

Massage with thumb and forefinger as needed



Marionette Lines with Radiesse

Samuel Lam, MD Dallas, TX

Before After 6 months0.4 cc per side

R. Allan Bexton, MDBakersfield, CA

Before After 3 Months(1.3 cc total)

Marionette Lines andMental Crease with Radiesse

Before After 10 months1.6 cc total

Peter Karlsberg, MD Ventura, CA

Marionette Lines with Radiesse

Pre-jowl Sulcus TechniqueLinear Threading

Pre-jowl Sulcus TechniqueLinear Threading

Robert Glasgold, MDHighland Park, NJ

Pre-Jowl Sulcus

Before After

Nasolabial Folds, Marionette Linesand Pre-Jowl Sulcus

Steven Dayan, MDChicago, IL

Before After 3 Months(3.9 cc total)

Progressive loss of fat within the face as a result of HAART therapy (Graded on a severity scale of 1-4 with 4 most severe)

Central facial hollows lateral to nasolabial folds

May involve volume loss in submalar, malar, infraorbital and temporal areas

Very psychologically and emotionally distressing

Immediately obvious in public as HIV sufferer

All social interactions are threatened

Radiesse can be used to re-volumize areas of deficiency to restore normal contours


Use 1.25” 27g or 25g needle

Provide adequate anesthesia- infraorbital, “mini-block” and field infiltration as needed

Insert needle into dermal/subcutaneous junction or subcutaneous space

Inject multiple threads of material using fanning technique to augment area

Layer additional threads of Radiesse into a deeper plane. Massage and mold with thumb and forefinger as needed.

Expect major improvement with 1-2 cc per side of face

Patients may require touch-ups and augmentation of additional areas as lipoatrophy progresses

HIV Facial LipoatrophySubmalar volume correction

HIV Facial LipoatrophySubmalar volume correction

In some cases, the malar area must also be augmented in lipoatrophy patients to restore normal volume

The entire zone must be addressed to provide volume and create a natural appearance

You are adding material to an area that has lost volume

Areas- Inferior lateral orbital rim

Malar eminence

Infraorbital hollow

Try to achieve a blending between the lower eyelid, nasolabial fold, and the cheek *For demonstration purposes, patient is not HIV+

HIV Facial LipoatrophyMalar and infraorbital volume correction

HIV Facial LipoatrophyMalar and infraorbital volume correction

HIV Facial LipoatrophyMalar, submalar and infraorbital volume correction

Courtesy of,Todd Owsley, MDGreensboro, NC

Todd Owsley, MDGreensboro, NC

Before After


Baseline Month 6

Month 12 Month 18

40 y/oMale

Total Volume8.0 mL


Immediate outcome : improvement immediate

Provides augmentation lasting a year or more in most patients

Swelling is to be expected, but resolves within hours

Adverse event profile is minor and similar to other injectables

The firmness of the injected material will soften by 2 wks and it will become like the resident soft tissue

The patients are ecstatic with the immediate result and this contributes to a positive quality of life


Summary

Radiesse is clinically proven to be safe. – It has been used on hundreds of thousands of patients

worldwide

– Zero granulomas in two separate 100+ patient FDA trials

Radiesse provides long lasting correction- about a year or more in most patients

Radiesse both fills and stimulates the body to produce new collagen with Calcium-based microspheres

Radiesse will grow your aesthetics practice with a wider range of applications

Radiesse is a better patient value– Greater patient satisfaction means more patients for you

Physician Reference Slides 2007. US Filler Market Evolution 2004 2006 FDA Approved December 2006 Wrinkles and Folds HIV Facial Lipoatrophy 1980’s Collagen.

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