Presentation given as part of Best Practices Meeting during 2012 DDW meeting in San Diego

1. LINX® Reflux Management System:
Best Practices Meeting
Friday, May18, 2012

2. Establishing the LINX® System as a Surgical
Offering
C. Daniel Smith, MD
Chair, Department of Surgery
Surgeon-in-Chief
Mayo Clinic in Florida

3. Disclosure
- Co-PI for one of the sites who participated in the
Pivotal Trial
- Advisor/consultant to Torax for preparation of the
presentation to FDA
- Joined company for presentation to FDA
- Paid consultant to company helping with safe
and successful introduction of Linx to care of
GERD patients

4. Goals for This Portion of Discussion
- I’m not going to tell anyone in audience anything
that they don’t already know
- Offer perspective on current surgical treatment
for GERD (Nissen fundoplication)
- Where would Linx fit in surgical practice
- What is the Linx patient
- Propose principles for use in our practices

5. Fundoplication
- Great operation
- Select patients do very well
- Superior to PPIs
- Significant positive impact on natural history of
GERD
- Multiple studies have confirmed its effectiveness
and role in treatment of GERD

6. Current Treatment Options for GERD
Fundoplication
Surgery
PPI Therapy PPI Therapy
No. GERD Patients
Fundoplication
Surgery
Severity of Symptoms and Dissatisfaction
Mild Severe

7. Fundoplication
- Use of fundoplication for GERD has peaked, use
has been slowly declining
- GIs have largely stopped referring patients
except for desperate or complicated cases
- Most cases are done for complicated conditions
(redo, large hiatal hernia, Barretts, severe
refractory GERD
- PPIs remain treatment of choice for all but the
most severe cases of GERD

8. Fundoplication – Why Not
- Multifactorial
- Technical failures – inconsistent and questionable outcomes
- Lack of standardized approach/technique
- Inconsistent use – patients still have fundoplication performed
without objective confirmation fo GERD
- Patients are afraid of the operation – troubling side-effects of
gas bloat and excess flatus or perception that failure rate is
50%
- GIs refuse to refer – all of the above and/or strong belief that it
is a bad operation
- Competing treatments – primarily PPIs, some endolumenal
approaches

11. Two Predictors of Surgical Outcome
Fundoplication
Patient Selection Operative Technique
• Patients without objective • 2 stitch, three stitch, four stitch
confirmation of GERD • Esophageal stitch, how many and
location
• Patients who fail to respond
• Pledgets for wrap or crural repair
to PPIs
• Divide short gastrics or not
• Patients with BMI >35 • Anchor wrap to diaphragm/crura
• Atypical symptoms? • Extensive esophageal mobilization
• Calibrate wrap and to what size
• Occasional antireflux surgeon • Occasional antireflux surgeon
• Patient selection can be tricky • Tricky operation
• Not everyone can get good
• Defining the typical GERD outcomes
patient has been difficult

12. Current Treatment Options for GERD
No standard treatment for Gap patients
Targeted Linx
PPI Therapy population
Therapy Gap
No. GERD Patients
Fundoplication
Surgery
Severity of Symptoms and Dissatisfaction
Mild Severe

13. Pivotal Trial
Key Outcomes

14. Summary of Efficacy Endpoints
Percent Successful (95% Binomial Exact Confidence Limits)
Primary: pH
Normalization or ≥ 64% (:54, 73%)
50% reduction
Secondary: GERD
≥ 50% reduction in 92% (85, 97%)
GERD-HRQL
Secondary: PPI
≥ 50% reduction in 93% (86, 97%)
daily PPI use
0 10 20 30 40 50 60 70 80 90 100

15. Efficacy Endpoints
by Baseline Hernia Assessment (≤3 cm)
Primary Efficacy Endpoint Component No Hernia All Patients
Normalization (pH<4.5%) 67% (29/43) 58.3% (56/96)
> 50% reduction from baseline 77% (33/43) 63.5% (61/96)
Either normalization or > 50% reduction 79% (34/43) 66.7% (64/96)

16. PPI Free Days
As of Last Follow-Up
900
800
700
600
PPI Free Days
500
400
300
200
100
0

17. 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

18. Reduced Gas Bloat
Severity of Gas Bloat
FREQUENTLY CONTINOUSLY
100
Percent of Patients Reporting
80
60
40
20
0
Baseline 12 Month Post LINX 24 Month Post LINX
Note: As actively queried by Foregut Questionnaire

19. Overall Acceptable Safety Risk
 144 patients implanted between 2-4 years
 No deaths
 No intra-operative complications
 No device failures
 No device erosions or migrations
Serious Adverse Events
 6% (8/144)
 No late onset (>1 year)

20. The Successful LINX Patient
Post-LINX
Baseline
% of Pts
% of Pts Characteristic
2 Years
100% Daily PPI dependence 8%
70% Reflux affecting their sleep on a daily basis 2%
76% Reflux affecting their food tolerances on a daily 2%
basis
57% Moderate or severe regurgitation including 1%
aspirations
55% Severe heartburn affecting their daily life 1%
51% Experiencing extra esophageal symptoms in addition 12%
to heartburn and/or regurgitation
40% Esophagitis 11%

21. How Were Good Results Achieved
• Rigorous adherence to patient selection and standardized
surgical technique (arguably, even tighter adherence to
standardized surgical technique would have improved
outcomes even further)
pH GERD-HRQL PPI Use
Hernia at Baseline N Endpoint Endpoint Endpoint
Success Success Success
None 44 77% 89% 91%
Yes – repaired 30 67% 100% 97%
Yes – not repaired 26 39% 89% 92%
pH Endpoint Success 95% CI
No hernia or hernia repaired 73.0% (54 / 74) 61.4, 82.7%

22. Two Predictors of Surgical Outcome
LINX
Patient Selection Operative Technique
• Tight control on patient • Device that results in
selection predictable
• Don’t go after extended
response/performance
inclusion criteria patients • Standard technique for
• Work closely with GI to assure placement
full diagnostic work-up and
consistent patient selection • If any question of hiatal
defect, approximate
• Consistent patient instructions
to establish expectations crura with stitch(es)
(dysphagia is common, diet
progression

23. Defining the LINX® Patient

24. Key Pivotal IDE Eligibility Criteria
Inclusion
 Age 18-75 years
 Typical GERD symptoms >6 months
 Pathologic GERD – (esophageal pH<4 for >4.5% of time)
 Daily PPI use
 Symptomatic improvement on PPIs
Exclusion
 Hiatal hernia (>3cm)
 Esophagitis Grade C or D (LA classification)
 Barrett’s esophagus
 Esophageal motility disorder

25. Patient Selection Per Labeling
INDICATION
The LINX Reflux Management System is indicated for patients
diagnosed with GERD as defined by abnormal pH testing, who
continue to have chronic GERD symptoms despite
maximum medical therapy for the treatment of reflux.

26. Patient Selection Per Labeling
PRECAUTIONS
1. Hiatal hernia >3 cm
These
2. Barrett’s esophagus
PRECAUTIONS are
3. Esophagitis grade C or D
based on the
inclusion/exclusion 4. Electrical implants or metallic abdominal implants
criteria of the 5. Major motility disorders
pivotal study. 6. Scleroderma
7. Esophageal or gastric cancer
Patients outside of 8. Dysphagia greater than once per week within the last 3 months
these 9. Esophageal or gastric surgery or endoscopic intervention
PRECAUTIONS have 10. Distal amplitude <35 mmHg or <70% peristaltic sequences
not been studied.
11. Esophageal stricture or gross anatomic abnormalities
12. Esophageal or gastric varices
13. Lactating, pregnant or plan to become pregnant
14. Morbid obesity (BMI >35)
15. Age <21 years

27. Extended Criteria Use
• Linx in hiatal hernia > 3 cm
• Linx in Barretts
• Linx in morbid obesity (BMI > 35)
• Linx with sleeve gastrectomy

28. Defining the LINX® Patient
Examples

29. Examples
• 45 year old male
• Heartburn is primary symptom
• Double dose PPI for last 3 years
• pH < 4.5 10%
• Normal esophageal motility
• Normal EGD
• 2 cm sliding hiatal hernia
• Completely satisfied on current PPI regimen
• LINX Patient?

30. Examples
• 24 year old female
• Chest pain is primary symptom
• Single dose PPI for last 6 months
• pH < 4.5 - 6%
• Normal esophageal motility
• Normal EGD
• Carries diagnosis of fibromyalgia
• Absolutely no improvement in GERD symptoms on
PPIs
• LINX Patient?

31. Examples
• 51 year old male
• Heartburn is primary symptom
• Single dose PPI for last 10 years
• pH < 4.5 - 11%
• Normal esophageal motility
• Normal EGD
• PPI controls heartburn symptom
• Recent onset of night time regurgitation
• 3 cm hiatal hernia
• LINX Patient?

32. Examples
• 58 year old female
• Heartburn is primary symptom
• Double dose PPI for last 10 years
• pH – Bravo has failed twice and can’t tolerate
catheter-based pH
• Normal esophageal motility
• Normal EGD
• PPI controls most of symptoms, some
breakthrough, concerned about osteoporosis and
reports of hip fracture when on PPIs
• No hiatal hernia
• LINX Patient?

33. Examples
• 72 year old male
• Chest pain and regurgitation are primary symptoms
• Double dose PPI for last 15 years
• pH < 4.5 – 8%
• Normal esophageal motility
• EGD with irregular SCJ – biopsy with non-dysplastic
Barretts
• History of short segment Barretts with – Halo
ablation 6 months earlier
• PPI does not control symptoms
• 3 hiatal hernia
• LINX Patient?

34. Examples
• 18 year old male
• Chest pain and heartburn
• Single dose PPI for last 2 years
• pH < 4.5 – 8%
• Normal esophageal motility
• EGD with eosinophilic esophagitis
• PPI does not control symptoms
• No hiatal hernia
• LINX Patient?

35. Examples
• 23 year old female
• Hoarseness and chronic cough are primary
symptoms
• Double dose PPI for last 5 years
• pH < 4.5 – 2% on PPIs, Impedence pH with non-acid
reflux episodes without correlation to symptoms
• Esophageal motility with disordered peristalsis, but
70% peristaltic and body pressure of 35 mm Hg
• EGD normal
• PPI helps some
• No hiatal hernia
• LINX Patient?

36. Summary / Principles
• Linx is a safe and effective tool for the management of
GERD
• In carefully selected patients outcomes are excellent
and reproducible across a variety of settings
• The maintenance of these good outcomes will be critical
to gaining acceptance and reimbursement for this
treatment option
• Tight adherence to strict work-up, selection criteria and
operative technique is critical to achieving the
consistent and good outcomes achieved in the Pivotal
Trial and needed for the ongoing success of this offering

37. Summary / Principles
• We should agree as thought leaders in the field to
adhere to these principles in offering Linx to our
patients
• Extended inclusion criteria use should be done through
agreed upon study so as to segregate data and
outcomes
• if we do this we can help assure the advancement of
our field through responsible introduction of new
techniques to clinical practice

38. Discussion