1. Other treatments for GERD… Lee L Swanstrom MD, FACS Division of Minimally Invasive Surgery Legacy Health System Portland, OR

2. flawed: Medical treatment of GERD is flawed: It is palliative only It doesn’t always work It doesn’t stop reflux It doesn’t alter the progression of Barrett’s to cancer It is expensive

3. PPI-associated Complications Increase Over Time Increased risk of acute coronary syndrome when used with Plavix 1 Increased gallbladder motility 2 Increased bacterial gastroenteritis 3 Increased risk of Clostridium difficile colitis 4 Decreased innate immunity 5 1 5 10 Years on PPI therapy References 1 Ho et al. JAMA 2009; 20:1364-7. 2 Cahan et al. Surg Endosc 2006; 20:1364-7. 3 Garcia Rodriguez et al. Clin Gastroenterol Hepatol 2007; 5:1418- 23. 4 Cadle et al. Am J Health Pharm 2007; 64:2359-2363. 5 Alkim et al. Dig Dis Sci 2008; 53:347-51. 6 Jalving et al. Aliment Pharmacol Ther 2006; 24:1341-8. 7 Targownik et al. CMAJ 2008;179:319-26. 8 Geevasinga et al. Clin Gastroenterol Hepatol 2006; 4:597-4. Increased renal failure 8 Increased risk of hip fracture 7 Increase of osteoporosis- associated fractures 7 4x the risk of gastric polyps 6

4. The problem with laparoscopic fundoplication… Can be dangerous Expensive ($13,500 at Legacy) Side effects can outweigh benefits for early or mild disease Not enough surgeons, ORs, time or energy to do lap Nissen on everyone

5. Other options? Gastric bypass Endoluminal treatments Gastric emptying Laparoscopic Prosthesis

6. Roux-en-Y Gastric Bypass Most frequently performed bariatric procedure in the US First done in 1967 Some technical modifications since (stomach is cut) Laparoscopically since 1993 60 –80% loss EBW 75 – 80% effective control of reflux

7. Endoluminal antireflux surgery: Radiofrequency ‘scarring’ of the LES (STRETTA) –FDA approved 2/20/00 Bard Sewing machine “endoplication” (Endocynch) –FDA approved 2/20/00 Endoscopic intramuscular injections (Enteryxx) –Approved under PMA 6/03 Transgastric / endoscopic repair (N-do) –National trials 9/03

8. Esophafix (Endogastric Solutions) “World's First Endoluminal Fundoplication” Brussels team performs world's first endoluminal fundoplication (100% trans-oral incision-less) with clinical aim of curing gastroesophageal reflux disease (GERD). Nissen

9. TIF Highlights TIF has been used in eight unbiased clinical studies Those clinical studies demonstrate that: –TIF is safe –TIF restores the GE valve anatomy and function –Results have been proven measuring: »Symptoms and quality of life »Use of PPIs »Impedance »pH-metry »Manometry –TIF2 improves on TIF1 –TIF is more effective than EndoCinch or Plicator Additional clinical studies on the TIF Procedure are underway

10. 10 Clinical Studies = 6 Completed + 4 In Progress Study (n) Available Data (n)Study StatusPublished TIF1: - Feasibility (19)2 yrs (14)Completed Yes - Multicenter (86)2 yrs (51)3-yr in progress No - Redo (15)6 mo (15) Completed No - Registry Fraser (20)7 mo (20) Completed No - Registry Bouvy (38)10 mo (38) Completed No TIF2: - Feasibility (10)6 mo (10) Completed Yes - Randomized vs. PPIs (120)6 mo (14) Enrolling n/a - Feasibility in children (14)3 mo (14)Completed n/a - RCT vs. Sham (60) n/a EC review n/a - RCT vs. LNF in children (300) n/a EC review n/a RCT –randomized controlled trial

11. Current strategy Chronic GERD symptoms Comprehensive evaluation [EGD, 24 hr pH, motility] Severe disease High DeMeester, esophagitis, Barrett’s, stricture, etc Mild disease Endoscopic ARS Laparoscopic ARS Breakthrough reflux post lap ARS

12. Highest Magnetic Resistance Lowest Magnetic Resistance Expands during swallow allowing food to enter stomach Reinforces the LES restoring the barrier function LINX™ Reflux Management System

13. LINX™ Design –Device Design Titanium beads with magnetic cores Linked together by titanium wires –Links limit expansion distance between beads –Resists sphincter relaxation while allowing normal physiological function (swallowing, belching, etc) –Mechanism of Action: Increased yield pressure of LES

14. Barium Swallow: 1 Day Post-Op

15. LINX™ Procedure DissectSizeSecurePlace

16. Healing Response: Porcine Explant (4 mo)

17. Clinical Outcomes - Feasibility 1 pH Normalization 79% No PPI Use89% Median HRQL Reduction96% 1 – Bonavina, J Gastrointetinal Surg. 2008 87% Reduction

18. Pivotal Trial Prospective, multi-center, single-arm study –Patient as their own control N=100 subjects Target Indication - subjects diagnosed with pathologic GERD as defined by abnormal pH scores and incomplete clinical response from medical therapy Primary endpoint –Normalized or >50% reduction in acid exposure @ 1 year Secondary Endpoints –>50% reduction in GERD HRQL @ 1 year –>50% reduction in PPI use @ 1 year

19. Conclusions: Reflux is a disease – it presents in a continuum of symptoms and causes. It varies with individuals Treatments must be individualized to the patient’s psychology and physiology