Ideal GERD Treatment

Restore LES barrier function

Preserve normal physiology

(ability to swallow, belch and vomit)

Provide consistent outcomes

Reversible if necessary

Outpatient procedure

There is no ‘Gold Standard’ approach

Issues with Fundoplication

Technically complex

Alters gastric anatomy

Operator-dependent

Side effects

Mostly used in complicated disease

Variable success rate*

*85% at 5 yrs (Lotus Trial, JAMA 2011)

A series of interlinked titanium beads, each of which with a magnetic core

Highest resistance when closed

The LINX® Reflux Management System

Initial pull apart force of 40 grams

Magnetic resistance to yield is the same for all size devices

Lowest resistance when expanded

Roman arch design

assures that the

device is non-

compressive when

closed

Titanium

case

Titanium

wire

Magnetic

core

LINX® Mechanism of Action

The LINX® Reflux Management System

LINX® Mechanism of Action

The LINX® Reflux Management System

LINX® Mechanism of Action

The LINX® Reflux Management System

LINX® System Preserves Physiologic Function

The LINX® Reflux Management System

Pivotal Trial Overview

Purpose To evaluate safety and effectiveness

Design Prospective, Multi-center, Single-arm

Control Subject as own control

Subjects 257 screened

100 implanted

Endpoint Analyses 12 months

Treatment Group (all implanted subjects)

Follow-up Discharge, 1wk, 3M, 6M, 12M – 60M (annually)

-Completed 24 months

-Subject Completion 12 months – 98%

24 months – 90%

NEJM Publication February 2013

GERD-HRQL Score off PPI G

ER

D H

RQ

L S

core

Off P

PI (M

ean) N=44

N=37 N=33 N=39 N=35 N=27

N=98 N=98 N=95

N=90

N=100

Elimination of Daily PPI Dependence

Free of Daily PPI Dependence

PPI Frequency of Use

Baseline 12 Months Post-LINX

24 Months Post-LINX

0% 91% 92%

Frequency Baseline 12 Months Post-LINX

24 Months Post-LINX

QD 64% 7% 7%

BID 35% 2% 1%

TID 1% 0% 0%

Sustained Control of GERD Symptoms

% of Patients ≥ 50% Reduction in GERD-HRQL

92% at 12 months

93% at 24 months

Sustained Control of Regurgitation

Note: As actively queried by Foregut Questionnaire

Control of Extra Esophageal Symptoms P

erc

ent

of

Patients

Report

ing

Note: As actively queried by Foregut Questionnaire

Pivotal Mean DeMeester Score Components

PARAMETER* N BASE-LINE

N 12

Month P VALUE

Total time pH<4 (%) 100 11.6 96 5.1 <.0001

Total upright time pH<4 (%) 100 14.0 96 6.5 <.0001

Total supine time pH<4 (%) 98 7.8 95 2.9 <.0001

Total number of reflux episodes 100 175 96 82.8 <.0001

Number of reflux episodes >5min 99 12.4 96 6.1 <.0001

Longest reflux episode (min) 99 37.4 96 19.7 <.0001

DeMeester Score 97 41.0 95 18.7 <.0001

*All pH testing completed with Bravo capsule endoscopically placed

Minimal Side Effects

Ability to Belch

• 99% of patients throughout study period

Inability to Vomit

• 0% at 12 months

• 1% at 24 months

Note: As actively queried by Foregut Questionnaire

Summary of Related Adverse Events

1 AEs with Frequency >5%

Adverse Event1 % Subjects

Dysphagia 68%

Pain 24%

Stomach Bloating 14%

Nausea 7%

Odynophagia 8%

Hiccups 8%

Inability to belch or vomit 6%

Dysphagia Observations

G Saino et al. Poster presentation at World Organisation for Specialized Studies on Diseases of the Esophagus 2012

THE LINX REFLUX MANAGEMENT SYSTEM: SAFETY AND EFFICACY RESULTS AT FOUR YEARS

THE LINX REFLUX MANAGEMENT SYSTEM: SAFETY AND EFFICACY RESULTS AT FOUR YEARS

G Saino et al. Poster presentation at World Organisation for Specialized Studies on Diseases of the Esophagus 2012

Acceptable Safety Profile Established

144 subjects with implant 2 to 4 years

No intra-operative complications

No reports of device migration, erosion or

device failures

AEs

4% Feasibility

6% Pivotal

One Hundred Consecutive Patients treated with Magnetic Sphincter

Augmentation for Gastroesophageal Reflux Disease: Six Years of Clinical Experience from a Single Center

Bonavina L, Saino G, Bona D, Sironi A, Lazzari V.

Corresponding Author: Luigi Bonavina, MD, FACS Email: luigi.bonavina@unimi.it

Magnetic Sphincter Augmentation

CLOSED – magnetic resistance

• Augments a weak LES

• Prevents opening of LES to gastric reflux

OPEN – least resistance

• Allows passage of food bolus

• Doesn’t inhibit belching and vomiting

Baseline Characteristics

Measure Group 1

Pts 1-25

Group 2

Pts 26-50

Group 3

Pts 51-75

Group 4

Pts 76-100

All

Patients

N=100

Age – years (Median) 45 39 45 33 44.5

Male - % 18 15 18 23 74

Female - % 7 10 7 2 26

BMI (Median) 24 22 24 25 24

Years with GERD 6 5 4 7 5.5

Years of PPI Use 5 4 4 5.5 4

Esophagitis (n)

None 18 22 22 21 83

Grade A/B 7 2 3 4 16

Grade C/D 0 1 0 0 1

Barrett’s Esophagus 0 1 1 0 2%

Hiatal Hernia Size

None 8 3 2 8 21

1-3 cm 17 21 23 16 77

>4 cm 0 1 0 1 2

DeMeester Score 30.4 36.0 37.4 29.7 33.4

GERD-HRQL Score Comparison at Baseline and Last-Follow-up

Improved Reflux Symptoms and Minimal Side Effects

Measure Baseline Last Follow-up

REGURGITATION

None 12% 85%

Mild 26% 10%

Moderate 59% 5%

Severe 3% 0%

Daily episodes 72% 2%

EXTRA-ESOPHAGEAL SYMPTOMS

None 48% 84%

Recurrent Cough 32% 11%

Nocturnal Cough 9% 2%

Asthma 9% 0%

Change of Voice 37% 2%

SIDE EFFECTS

Gas Bloat§ 48% 2%

Dysphagia§ 8% 0%

Odynophagia§ 4% 0%

Ability to belch 100% 99%

Ability to vomit 100% 99%

Percentages may not total 100 because of rounding. NA denotes no assessment completed per protocol at time point. * Scores range from 0 to 50, with higher scores indicating worse symptoms. †Patients 31-100 completed the GERD-HRQL while on PPIs at baseline and off PPIs at follow-up

‡ Patients 1-30 completed the GERD-HRQL while off PPIs at baseline and follow-up

§Percentage of patients reporting a score >3 on the GERD-HRQL for the corresponding question.

% of Patients with PPI Use

GERD-HRQL Score (Median)

Clinical Outcomes by Implant Group

Understanding Patient Perceptions about Antireflux Surgery

QUESTION RESPONSE % of PATIENTS

Why did you decide to

undergo surgery?

Drug therapy only partially effective

Poor quality of life

Fear of cancer

77%

8%

14%

Where did you learn about

LINX, who sent you to us?

Referring physician

Internet/Press

64%

36%

Would you undergo the

operation again?

Yes

No

91%

9%

Would recommend it to a

friend?

Yes

No

94%

6%

What did you hear about

Nissen fundoplication?

Effective only in the short-term

Too invasive

Dysphagia

Inability to belch/vomit

Not reversible

90%

90%

75%

60%

41%

Conclusions

• Based on 100 consecutive patients treated over a 6 year period, magnetic sphincter augmentation has shown its ability to safely improve reflux symptoms and allow discontinuation of PPIs, with no or minimal side effects.

• The minimal side effects seen after magnetic sphincter augmentation adds to the clinical value of this procedure and acceptance by patients.

• With the standardization of magnetic sphincter augmentation, it is possible that the variability in outcomes observed with traditional antireflux surgery can be significantly reduced.

• Magnetic sphincter augmentation represents the first major advancement for antireflux surgery in decades, and is a much needed alternative treatment for patients with reflux disease refractory to medical therapy.

Conclusion / Observations

Device closely reproduces native LES function - dynamic

Improvement over current surgical options Very few can perform a good fundoplication – tricky operation

Greatly ameliorates the side effects

Low complications and favorable pattern of failure

Addresses a significant unmet need

Positively transforms patients’ lives

LINX would be a tremendous positive addition to current options for GERD

Experience to date

First implant February 2007 (Milan)

Clinical implants;

Feasibility study 44

Pivotal study 100

Commercial implants >1,500

37 European implanting centres

50 US Implanting centres