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Overview of Sonography-Guided

Transcervical Fibroid Ablation

David Toub, MD

Medical Director, Gynesonics

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The Need for a New Treatment Option for Symptomatic Fibroids

In a published national survey of affected women:1

Women delayed seeking treatment for an average of 3.6 years, with 32%

waiting more than five years.

79% of women want to avoid invasive surgery that can require lengthy

recoveries.

Women of all ages are asking for alternatives to hysterectomy and want a

uterus-preserving treatment option regardless of their desire for

childbearing.

1) Borah BJ, Nicholson WK, Bradley L, Stewart EA. The impact of uterine leiomyomas: a national survey of affected women. Am J Obstet Gynecol. Oct 2013;209(4):319 e1-319 e20.

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Transcervical Fibroid Ablation (TFA)

Volumetric, image-guided radiofrequency ablation

Enables optimized ablated volume of targeted fibroid

Avoids multiple passes of energized needles through the serosa

Not a global therapy; can treat the fibroids that are likely to be symptomatic

Incites thermal fixation and coagulative necrosis

Not associated with infarction-related post-embolization syndrome.

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Sonata Transcervical Fibroid Ablation System

FDA cleared and CE marked

Uses radiofrequency (RF) energy to ablate fibroids

under real-time intrauterine sonography (integrated

within device)

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Intended UseThe Sonata System is intended for diagnostic intrauterine imaging and transcervical treatment

of symptomatic uterine fibroids, including those associated with heavy menstrual bleeding.

Contraindications

Current pregnancy; active pelvic infection; known or suspected gynecologic malignancy or premalignant disorders such as atypical endometrial hyperplasia;

presence of one or more intratubal implants for sterilization; and presence of an intrauterine device (IUD), unless removed prior to the introduction of the

Sonata Treatment Device.

Patient Selection Considerations

Safety and effectiveness with regard to fertility and fecundity after the use of the Sonata System have not been established, and effectiveness in women with

clinically significant adenomyosis has not been established.

Anticipated Postoperative Events and Potential Risks

Anticipated postoperative events include: abdominopelvic pain/cramping; back pain; constipation; dizziness/fatigue; headache; fever; malaise;

nausea/vomiting; sloughing and, less commonly, intact expulsion of ablated fibroid tissue per vaginam (particularly after ablation of submucous fibroids),

and vaginal spotting/bleeding/dysmenorrhea. Potential risks associated with fibroid ablation using the Sonata System include: allergic reactions (including

rash) to device materials; bowel or bladder perforation; cervical/vaginal laceration or tear; dysmenorrhea; electrical shock; hematometrium; hemorrhage;

infections: major and minor local and systemic infections, including intrauterine infection; retention of device fragment; skin burn from the dispersion of RF

energy; thrombotic events; unintended injury to the uterus, cervix or vaginal vault, adjacent organs or tissue; unknown risk to future pregnancies; and

complications including death.

To learn more about the Sonata System, visit us at gynesonics.com/sonata-system or sonatatreatment.com

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Sonata System Technology

Sonata System Hardware and Software

No manual measurements - all done graphically

Scalable ablations up to 49mm x 42mm

1.5 to 7-minute ablation times

RF generator modulates power (≤ 150W) to

keep electrode tip temperatures ~105 C

Sonata Treatment Device

Combines intrauterine ultrasound with

delivery of RF energy

8.3 mm tip diameter (27 Fr dilatation)

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SMART Guide: Graphical Overlays on Live Ultrasound Image

IUUS Probe Tip

Ablation Zone

Thermal Safety

Border

Ablation Zone: (red inner ellipse)

A graphical representation of the average

region of tissue ablation.

Thermal Safety Border: (green outer ellipse)

The distance at which tissue is safe from

potential of thermal damage.

9 | ML 06072 -001.B *Data on file at Gynesonics. MTF 190719-01

No Manual Measurements Necessary with SMART Guide

Algorithms used to display the SMART Guide were developed and validated by 1,928

clinical and bench tests including direct uterine serosal temperature measurements.*

Tissue is safe from any treatment effect at or beyond the Thermal Safety Border.

The size and position of

the Ablation Zone is

selected by the

gynecologist under

real-time ultrasound

guidance.

The Thermal Safety

Border adjusts

automatically to

correspond with

changes to the

Ablation Zone.

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100% fibroid volume ablated

Predictable Targeting and Optimized Fibroid Volume Ablation

Fibroids were treated transcervically with the

Sonata System prior to elective hysterectomy

two weeks later.

The treating gynecologist utilized the SMART

Guide to target fibroids.

Uteri were sectioned and ablations assessed.

Pathologists found that ablations were located

and sized as predicted.

Full Reference: Garza-Leal, JG, Toub, D, León, IH, et al. Transcervical, intrauterine ultrasound-guided radiofrequency ablation of uterine fibroids with the VizAblate System: safety, tolerability, and ablation

results in a closed abdomen setting. Gynecol Surg (2011) 8: 327.

90% fibroid volume ablated

Viable, non-ablated fibroid

tissue.

Fibroid B:

4.1 x 3.7 x 3.8 cm Fibroid A:

2.8 x 2.5 x 2.1 cm

Ablated fibroid tissue.

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Designed to Treat All Non-Pedunculated Uterine Fibroid Types

The Sonata System is designed to ablate or

partially ablate the target fibroids in GREEN

FIGO Leiomyoma Subclassification System

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The FAST-EU trial:

12-month clinical outcomes of women

after intrauterine sonography-guided

transcervical radiofrequency ablation

of uterine fibroids.

Brölmann H, Bongers M, Garza-Leal JG et al.

Gynecol Surg. 2016; 13: 27-35.

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Brölmann H, Bongers M, Garza-Leal JG

et al. The FAST-EU trial: 12-month

clinical outcomes of women after

intrauterine sonography-guided

transcervical radiofrequency ablation

of uterine fibroids. Gynecol Surg. 2016;

13: 27-35.

Baseline 3-months 12-months

Time course series on MR, courtesy of Jose Gerardo Garza-Leal, MD

FAST-EU

Clinical Trial

Objective To establish the safety and effectiveness of the Sonata

System in the treatment of symptomatic uterine fibroids

Study Design ▪ 50 patients treated at 7 centers in Europe and Mexico

3-months ▪ 90% of patients had a reduction in menstrual bleeding

12-months

▪ 92% of patients were free from surgical reintervention

for heavy menstrual bleeding

▪ 54% mean reduction in menstrual bleeding

▪ 67% mean reduction in fibroid volume

▪ 88% overall patient satisfaction

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The SONATA Pivotal IDE Trial:

Ultrasound-Guided Transcervical Ablation of

Uterine Leiomyomas

12-Month Results

Chudnoff S, Guido R, Roy K, Levine D, Mihalov L,

Garza-Leal JG. Obstetrics & Gynecology. 2019; 133: 13-22.

Transcervical Radiofrequency Ablation of

Symptomatic Uterine Fibroids:

2-Year Results

Miller CE, Osman KM, J Gynecol Surg

2019; 35:345-349

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12 Month Results

Chudnoff S, Guido R, Roy K, et al.

Ultrasound-Guided Transcervical Ablation of

Uterine Leiomyomas. Obstet Gynecol; 2019;

133: 13-22.

2-Year Results

Miller CE, Osman KM, Transcervical

Radiofrequency Ablation of Symptomatic

Uterine Fibroids: 2-Year Results of the

SONATA Pivotal Trial

J Gynecol Surg 2019; 35:345-349

SONATA

Pivotal IDE TrialObjective To establish the safety and effectiveness of the Sonata System

in the treatment of symptomatic uterine fibroids

Study Design Prospective, longitudinal, multicenter, single-arm

interventional study. 22 sites with 147 patients treated.

Subjects followed at 10 days, 30 days, 3, 6, 12, 24 and 36

months.

Co-Primary

Endpoints

Reduction in menstrual blood loss (MBL) as assessed by

pictorial blood loss assessment chart (PBAC)

Rate of surgical reintervention for heavy menstrual bleeding

(HMB) due to treatment failure

Quality of Life

Measures

Patient-reported outcomes included the Uterine Fibroid

Symptom Health-Related Quality of Life Questionnaire (UFS-

QOL) and the Overall Treatment Effect Questionnaire (OTE)

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Treatment Summary, Procedure Time, and Length of Stay

Total Fibroids Ablated 442

Mean # Ablated Fibroids per Patient 3.0 (range:1-9)

Mean # Ablations per Fibroid 1.1 ± 0.4

Procedure Time (minutes)(time elapsed from insertion of device to removal of device)

Median

40.0 min Mean

46.9 ± 29.7min

Length of Stay (hours)(time elapsed from insertion of device to time of discharge)

Median

2.3 hours

Mean

2.5 ± 1.2

Return to Normal Activity (days)Median

1 day

Mean

2.2 ± 2.2

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Well-Tolerated Procedure with Choice of Anesthesia

*pain scores captured on a 0-10 scale

Anesthesia Regimen

% of patients who underwent GA 50.3%

% of patients who had CS 49.7%

Mean Pain* During Procedure

GA .01

CS .47

Mean Pain* During Recovery

GA 3.4

CS 1.9

Patients Who Found the Procedure Tolerable 98%

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80% of Fibroids Treated in SONATA Trial were NOT Amenable to

Treatment with Operative Hysteroscopy

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Significant Reduction in Menstrual Bleeding

through 12 Months

303.6

175.9159.5

143.8

0

50

100

150

200

250

300

350

Baseline 3M 6M 12M

Mean Pictorial Blood Loss Assessment Chart (PBAC)

All p < 0.001

-39% -48% -51%

▪ 86% of patients reported a reduction

in menstrual bleeding at 3 months

post-procedure.

▪ 95% of patients reported a reduction

in menstrual bleeding at 12 months

▪ 65% of women reported >50%

reduction in menstrual bleeding.

▪ Sonata was effective in patients

where their only qualifying fibroid

was one or more intramural type 3.

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Safety Profile

▪ No device-related Serious Adverse Events (SAEs)

▪ 2 procedure-related SAEs; both resolved with no sequelae

▪ DVT 15 days post-procedure

▪ Vaginal discharge with low-grade fever and cramping 28 days post-procedure

▪ Overnight hospital stay for antibiotic administration per hospital policy

▪ Cultures negative for infection

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Rapid Return to Normal Activity and Work

▪ 50% of patients returned to normal activity

by the next dayOn average, patients resumed normal

functions:

▪ Diet at 0.8 ± 1.3 days

▪ Sleep at 0.7 ± 1.6 days

▪ Urinary function at 0.2 ± 0.8 days

▪ Bowel function at 1.4 ± 1.9 days

▪ Mean return to normal activity: 2.2 days ± 2.2 days

▪ Mean return to work: 3.6 ± 2.6 days

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Timepoint

Cumulative

Surgical

Reinterventions

Cumulative Surgical

Reintervention Rate

(Binomial)

Cumulative Surgical

Reintervention Rate

(Life-Table)

Cumulative Surgical

Reintervention Rate

(Kaplan-Meier)

1 Year 1 0.7% 0.7% 0.7%

2 Year 7 5.5% 5.2% 5.0%

3 Year 11 9.2% 8.5% 8.2%

Low Rate of Surgical Reintervention for HMB through 3 Years

Surgical reintervention rates remained low through 3 years regardless of statistical analysis methods.

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Improvements in Work and Activity Impairment

Maintained through 3 Years

All p-values < 0.001 compared to baseline

50.9%

57.9%

11.4% 11.7%14.6% 13.7%12.5%

14.3%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

Overall Work Impairment

(absenteeism + presenteeism)

Activity Impairment

Me

an

Wo

rk a

nd

Act

ivit

y I

mp

air

me

nt

Baseline 12M 24M 36M

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Significant Quality of Life Improvements Persist

Through 3 Years

All p-values < 0.001 compared to baseline

54.9

26.922.7 22.6 23.7 22.2

40.3

77.9

84.0 84.2 82.7 83.1

0.0

20.0

40.0

60.0

80.0

100.0

Baseline 3M 6M 12M 24M 36M

SSS HR-QoL

Symptom Severity Score (SSS) and Health Related Quality of Life (HR-QoL) Outcomes

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Bongers M, Quinn SD, Mueller MD,

et al. Evaluation of Uterine Patency

following Sonography-Guided

Transcervical Ablation of Fibroids.

Eur J Obstet Gynecol Reprod Biol.

2019;242:122-125.

OPEN Trial

Objective Characterize incidence of new intrauterine adhesions following

Sonata treatment

Study Design Post-market, prospective, multicenter, single-arm, observational

study in Europe. Indenting fibroid required for inclusion.

• Hysteroscopic assessment at baseline and 6-weeks

Endpoint Incidence of new adhesions at 6 weeks per European Society of

Hysteroscopy adhesion scoring by independent readers

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OPEN Trial Results:

No Adhesiogenesis After Treatment

37 patients enrolled at 6 sites

Mean patient age: 42.4 ± 7.2 years (range 29-55)

Mean ablated fibroid diameter: 3.2 ± 1.6 cm (range 1-8 cm)

2 patients withdrew prior to follow-up

35 pairs of baseline and follow-up hysteroscopies

were evaluated by independent readers.

1 patient video was unevaluable (no agreement in evaluation

by any of the 3 independent readers)

34 showed no sign of adhesions after Sonata per agreement in

evaluation by 2 independent readers

6 out of 34 patients had apposing submucous fibroids ablated

with no resulting adhesions

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Systematic Review and Meta-analysis of Studies

Radiofrequency Ablation of Uterine Fibroids

Bradley LD, Pasic RP, Miller LE. Clinical Performance of Radiofrequency Ablation for Treatment of Uterine Fibroids: Systematic Review and Meta-Analysis

of Prospective Studies. J Laparoendosc Adv Surg Tech A. 2019;1507-1517.

OBJECTIVETo examine the evidence regarding typical patient outcomes

with radiofrequency ablation (RFA)

OUTCOMES

FOR ANALYSIS

• Procedure time and patient recovery metrics

• Change in fibroid volume

• Symptom Severity Scores and Health-Related QOL Scores

• Reinterventions

N=32 articles

1283 unique patients

CONCLUSIONS

Radiofrequency ablation (RFA) of uterine fibroids significantly

reduces fibroid volume, provides significant durable improve-

ments in fibroid-related quality of life and is associated with

favorable reintervention rates.

REPORTED KEY

OUTCOMES

LAPAROSCOPIC

APPROACH

TRANSCERVICAL

APPROACH

Mean procedure

time73 min 44 min

Mean time to

discharge10.7 hours 2.5 hours

Mean return to

normal activities9.0 days 3.3 days

Mean time to

return to work6.5 days 3.6 days

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Summary of Key Outcomes

Outcomes associated with sonography-guided transcervical fibroid ablation

(TFA) to treat symptomatic uterine fibroids:

A significant reduction in mean menstrual bleeding

Low surgical reintervention for HMB

Well tolerated by patients with rapid return to normal activity

Significant and durable improvements in fibroid symptoms and health-related

quality of life

High patient satisfaction and willingness to recommend this treatment

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THANK YOU!