PN: C00771-01 B

Current Indications for

Endoscopic Transoral Incisionless Fundoplication - TIF

Stefan J.M. Kraemer, M.D.skraemer@endogastricsolutions.com

July 24, 2008

                      

                      

                      

                      

Topics

• Key Aspects of GERD?

• Scope of the Disease

• Current Treatments and Surgical Options

• Surgery –TIF (Natural Orifice Surgery)– Transoral Incision-less Fundoplication (EsophyX)

• Patient Profile and Patient Experience

                      

                      

                      

                      

What Causes GERD?

• Esophageal dysmotility

• Inadequate saliva production

– Saliva normally “buffers” any acid

• Impaired resistance of esophageal lining against acid

• Lower Esophageal Sphincter (LES) dysfunction

– Poorly functioning sphincter muscle

• Gastroesophageal Junction (GEJ) incompetent

– Gate between stomach and esophagus allows acid to wash up into esophagus

                      

                      

                      

                      

What Causes GERD?

• Delayed emptying of stomach– Poor motor function of

stomach allows acid to “pool” in stomach

• Hiatal hernia – Allows acid to reflux up into

the esophagus

                      

                      

                      

                      

But the Root Cause in Moderate/Severe GERD is Anatomical changes

(LES)

Angle of HIS

Fundus

Diaphragm

Z- Line

(LES)

Angle of HIS

Fundus

Gastroesophageal Flap Valve (GEV)

Esophagus Diaphragm

Z- Line

Lower Esophageal Sphincter

Normal AnatomyGERD

                      

                      

                      

                      

Mechanism and Progression of GERD

Mild Severe

                      

                      

                      

                      

Reflux Affects Lifestyle

• 40% of population suffers from heartburn at least once a month

• Incidence of GERD rises rapidly over age 40

• Sleep Deprivation– Daytime Sleepiness

– Auto Accidents, Productivity

• Progressive Disease if left untreated:– Herniation

– Barrett’s Esophagus

– Esophagial Cancer 15 Million Patients suffer from GERD Daily

                      

                      

                      

                      

Patients Dissatisfied with PPIs > 20-40% * of patients are not satisfied with PPI

medication> Patients not responsive to PPIs (Non-responders)> Patients on PPIs but lifestyle is still impacted

• Night time symptoms still persist*> Patients with small hiatal hernia aggravating

GERD> Persistent regurgitation> Patients with extraesophageal manifestation

of GERD• Asthma, Cough, Hoarseness, Dental, ENT problems

*Gallup Poll 2000 for AGA N=1000 American Journal of Gastroenterology 2003; vol. 98 Shaker et al

Patients needing a new approach

                      

                      

                      

                      

Excellent Results for Curing Esophagitis and Ulcer

Loss of efficacyLoss of efficacySide-effects such as dry mouthSide-effects such as dry mouthCalcium and Iron absorption Calcium and Iron absorption

Gastric polypsGastric polypsBacterial gastroenteritisBacterial gastroenteritis

Unclear cancer riskUnclear cancer riskOnly short-term indication clearedOnly short-term indication cleared

PPIs Under Increasing Pressure

                      

                      

                      

                      

Lundell et al. British Journal of Surgery 2007; 94: 198-203

Conclusion: After 7 years, surgery was more effective in controlling overall symptomsof chronic GERD, but specific post-fundoplication complaints remained a problem.

With Clinical Data of TIF Approaching Reported Data on With Clinical Data of TIF Approaching Reported Data on LARS…LARS…

                      

                      

                      

                      

· EsophyX allows surgeon to operate remotely enabling incisionless surgery.

The EsophyX Approach

Transoral Surgery> No incisions

> No scarring

> No incisional herniation

> Less potential for infection - nosocomial infection minimized

> Patient friendly – easier to market

> Natural Orifice Surgery is the future

Unique Surgical Approach

                      

                      

                      

                      

· TIF2 Reconstructs the primary components of the GEJ impacting the entire ARB

TIF 2Transoral Incisionless Fundoplication

> 3rd generation in reflux surgery

> An evolution of current surgical procedures

> Based upon long standing surgical principles

> Physiological less invasive

> Surgical reconstruction transoraly

> Future options open – adjustable

> Adaptive to patients anatomy

Unique Surgical Approach

The EsophyX Approach

                      

                      

                      

                      

PharmaceuticalSurgical

“Front Line Surgical Management”

Lifestyle change

Severe GERD

Mild GERD

CHALLENGES:Large Hiatal Hernias

Risk Low

BENEFITS: GEJ reconstructed

PPIs reducedCan correct EsophagitisHiatal Hernia fixed < 2cm

Significant pH NormalizationImproved Quality of LifeReduce/Eliminate reflux

Adjustment possibleBenefit Med/High

*Gallup Poll 2000 for AGA N=1000 American Journal of Gastroenterology 2003; vol. 98 Shaker et al

>20-40% of patients are not happy with PPI medication*

Limitations of Rx• Do not stop reflux • Do not treat Atypical Symptoms

GERD Treatment Options

EsophyX

Functional Change Anatomic Change

                      

                      

                      

                      

EsophyX Animation

Unique Surgical Approach

                      

                      

                      

                      

Pre-TIF 2.0Post- TIF 2.0

                      

                      

                      

                      

NissenFundoplication

EsophyXFundoplicatio

nRecreates Angle of HIS Yes YesInvolves multiple sutures/fasteners

Yes Yes

Reduces Hiatal Hernia Yes YesCreates a substantive nipple valve

Yes Yes

Lengthens Intraabdominal Esophagus

Yes Yes

Tighten LES/high pressure zone

Yes Yes

GEV anchored Yes YesCrura closed Yes NoUndone/redone** Yes

**Avoided -Invasive/complicated

Yes

Can be revised (adjusted) No Yes

Incisionless No YesNoninvasive no dissection No Yes

>Serosa-to-Serosa fusion

Transoral Surgery – “internal” – truly noninvasive

Based upon the surgical repair principles

of the gastroesophageal junction

Unique Surgical Approach

NEXT generation NEXT generation in surgery NOSin surgery NOS

                      

                      

                      

                      

Multi Center Trial (1year) N=79

Clinically Safe & Effective

85% of Patients OFF daily PPI’s

> Comparable efficacy & better tolerated then LNF

> No significant dysphagia, diarrhea, gas bloat

> Excellent QOL improvement 73%

> Elimination of PPI use 85%

> Esophagitis resolution 59%

> Hiatal hernia reduction 71%

> pH normalization 48% (Hill

grade one)

                      

                      

                      

                      

Phase 2 – Dietary Changes Favor ELF Over PPIs

• Benefit of ELF over PPIs are supported by increased consumption of reflux-inducing food items without GERD symptoms

• Patients’ tolerance for dietary challenging food items12 mo. after ELF exceeds benefits patients experienced on PPIs

0%

20%

40%

60%

80%

100%

Citrus*

Strawberries*

Tomatoes*

Chocolate*

Fatty Foods*

Deep-Fried Foods*

Spicy Foods*

Carbonated Drinks*

Tea*

Coffee*

Caffeinated Drinks*

Alcohol*

12 mo Post-TIF Pre-TIF OFF PPIs

*P < 0.01

0%

20%

40%

60%

80%

100%

Citrus*

Strawberries

Tomatoes

Chocolate

Fatty Foods

Deep-Fried Foods

Spicy Foods

Carbonated Drinks*

Tea

Coffee*

Caffeinated Drinks

Alcohol*

12 mo Post-TIF Pre-TIF ON PPIs

                      

                      

                      

                      

Clinical Effectiveness

ELF1.0 ELF1.0 TIF 2.0 PPIs LNF Toupet

Hill I Tight

GERD-HRQL improved by ≥ 50%

73% 75% 88% 68-91% 61-97% 61-97% (from Nissen)

Off daily PPIs 85% 86% 70% 0% 79-100% 65-92%

Normal acid exposure

37% 48% 67% 50-92% 88-97% 49-94%

Esophagitis reduced

62% 80% 67% 84-94% 86-95% 82-89%

Hiatal hernia reduced

60% 89% 89% 0% 87-99% 95%

                      

                      

                      

                      

TIF Evolution Yields Surgery-Like Results

                      

                      

                      

                      

EsophyX Experience

• 45 - 60 minute procedure• Proven 3rd Generation Technology• Overnight stay (general anesthesia)• Rapid Recovery• Incisionless• Reversible, Revisable, Re-doable

Unique Surgical Approach

                      

                      

                      

                      

Patients with gastroesophageal reflux disease (GERD) that is unresponsive to daily proton pump inhibitor (PPI) therapy

Patients with ARB deterioration

Patients not satisfied with their current medical management

Young patients with a long-term future of medication

Patients with GERD who want to discontinue daily PPI use

Patients with atypical symptoms, including laryngopharyngeal reflux (LPR) indicated by chronic or intermittent hoarseness, chronic throat clearing, chronic cough, voice fatigue or changes, globus sensation, and sore throat.

Profiles for Referral

                      

                      

                      

                      

Pharmaceutical

Palliation; treatment of esophagitis and ulcer

Surgical

Treatment of anatomical root cause

Severe GERD

Hiatal hernia

Mild GERD

Before EsophyX 12 mo after EsophyX

Functional Change Anatomic Change

Mechanism and Progression of GERD

Tranoral Incsionless Fundoplication TIF2

PN: C00771-01 B

EsophyX Getting it Right