aptus heli-fx overview physician slide deck developed by aptus endosystems, inc. mma05141501

Aptus Heli-FX Overview Physician Slide Deck Developed by Aptus Endosystems, Inc. MMA05141501

R.M. Greenhalgh et al. N Engl J Med 2010, 10.1056/NEJM 0909305 De Bruin et al. N Engl J Med 2010;362:1881-9 Major Studies Show Higher 2 nd Interventions in EVAR vs. Open Repair Late ruptures in EVAR, none in open surgery Unlike open repair, endoleaks and migration are major complications of EVAR Predictors for rupture, and risks increase with time Open surgery remains a more durable option In ACE, 16% re-interventions in EVAR vs. 2.4% for open repair at 3 yr median f/u Becquemin JP et al. J Vasc Surg 2011;53(5):1163-73. DREAM EVAR-1 ACE 2

StudySample SizeEndografts Torsello et al, 2011177Endurant AbuRahma et al, 2010238AneuRx, Excluder, Zenith, Talent Hoshina et al, 2010129Excluder, Zenith Abbruzzese et al, 2008565AneuRx, Excluder, Zenith Choke et al, 2006147Talent, Zenith, Excluder, AneuRx Fulton et al, 200684AneuRx Fairman et al, 2004219Talent Meta-Analysis of 7 major studies in EVAR by Antoniou et al 1 compared outcomes in hostile vs. friendly neck anatomies (total patients N = 1559) 1 Antoniou GA et al. J Vasc Surg. 2013;57(2):527-38. Type I endoleaks 4.5x more likely at 1-year after endograft implantation in hostile proximal aortic neck anatomy (P =.010) Aneurysm-related mortality risk 9x greater in hostile neck anatomy (P=.013) 3 Hostile Proximal Necks Further Challenge EVAR

Another similar meta-analysis by Stather et al. of 16 major studies confirms higher risks in hostile necks Further substantiation that EVAR still faces significant challenges in hostile proximal neck anatomy Stather PW et al. J Endovasc Ther. 2013;20:623637 Total sample size: N=11,959 patients Hostile Proximal Necks Further Challenge EVAR 4

Neck hostility Intra-op adjunctive procedures Intra-op endoleaks All cause mortality On label 9.9%0.5%1.1% 2 hostile neck parameters 26.7%6.7%13.3% >2 hostile neck parameters 50%16.7% Speziale et al. shows greater proximal seal complication risks as the number of hostile neck parameters increases Speziale F et al, Annals of Vascular Surgery (2014), doi: 10.1016/j.avsg.2014.06.057. Greater than 1 hostile neck parameter substantially increases mortality, major adverse events, intra-op endoleaks and adjunctive procedures Influence of Multiple Hostile Neck Parameters 5

Which Proximal Necks are Hostile? Study by Jordan WD et al. assesses proximal neck anatomic criteria that are most predictive of success or failure after EVAR Evaluated N=221 patients from ANCHOR post-market registry Failure defined as: Type Ia endoleak upon endograft implantation Type Ia endoleak identified in post-op follow-up* *In endografts without EndoAnchors Identified proximal neck variables that independently predict type Ia endoleak: Neck diameter 26 mmP =.002 Neck length 17 mmP =.017 Certain on-label necks can be at-risk Jordan WD et al. J Vasc Surg. 2015 Feb 28. pii: S0741-5214(15)00065-8. 6

AuthorFollow- Up Grafts studiedProximal Neck Dilatation Rate Outcomes in dilated necks Oberhuber et al. 1 39 mos average Zenith (N=29), Talent (N=35), Excluder (N=39) 22% (defined as >2mm diam increase) 31% re-interventions Pintoux et al. 2 57 mos average Talent (N=33), AneuRx (N=25) 24% (defined as >3mm diam increase) 5% late type Ia endoleak 16% migration Bastos Gonalves et al. 3 5 yrs median Excluder (N=144)37% overall, 66% in pts >7 yrs f/u (defined as >2mm diam increase) Increased odds of migration (5mm) 5.5x 1 Oberhuber A et al. J Vasc Surg 2012 April;55(4): 929-34 2 Pintoux D et al. Ann Vasc Surg. 2011 Nov;25(8):1012-9 3 Bastos Goncalves F et al. J Vasc Surg. 2012 Oct;56(4):920-8 Multiple recent studies confirm neck dilatation in EVAR remains REAL Neck Dilatation: A Cause for 2 nd Intervention 7

1.Nordon IM et al. Eur J Vasc Endovasc Surg 2010;39(5):547-54. 2.Dias NV et al. Eur J Vasc Endovasc Surg 2009;37(4):425-30. Compromise of EVAR and Long-Term F/U 8

Image courtesy of National Institute of Health AAA ClassificationPossible TI EL TX Options Infra-renalEVAR Revision*, open surgical conversion, FEVAR conversion Juxta-renalOpen surgical conversion, FEVAR conversion, CHIMPs Supra-renalOpen surgical conversion, FEVAR conversion, CHIMPs TAA ClassificationPossible TI EL TX Options AscendingOpen surgical conversion Aortic ArchTEVAR Revision*, hybrid DescendingTEVAR Revision* *Ballooning, cuffs, Palmaz, coils, Onyx and/or CHIMPs may be considered in EVAR/TEVAR revision Type I Endoleak? What Have Been Our Options What do we do when? Standard revision techniques cannot be used or dont seal endoleak? Patients are unfit for FEVAR or open surgical conversion? Image courtesy of National Institute of Health 9

EndoAnchoringSurgical Anastomosis Case images courtesy of John Aruny MD, Bart Edward Muhs, MD, PhD. Tailored Seal and Fixation of EndoAnchors CREATE THE STABILITY OF A SURGICAL ANASTOMOSIS IN EVAR AND TEVAR Displacement force in Newtons Chart from data published in Melas N, et al. J Vasc Surg 2012;55(6):1726-33 10

Replicate surgical anastomosis Prevent late term seal complications in primary setting Treat seal complications & prevent recurrence in revision setting Mitigate reinterventions in EVAR Improve surveillance intervals by preventing type I leaks and sac growth Long-Term Objectives of EndoAnchors in EVAR 11 Completed In-process Next phase Legend: Status of clinical substantiation

Intended to provide fixation and augment sealing between endovascular aortic grafts and the aorta Indicated for use in patients whose endovascular grafts have exhibited migration or endoleak, or are at risk of such complications The Aptus EndoAnchor and Heli-FX have been evaluated and determined to be compatible with the following endografts: Heli-FX Indications for Use (FDA and CE Mark) 12 Cook Zenith Gore Excluder Medtronic AneuRx Medtronic Endurant Medtronic Talent Jotec GmbH

TREATMENTPROPHYLAXIS Hostile Anatomy Overcoming concerns for implant stability Challenging neck anatomies (e.g. wide, short, conical, angulated) Difficult landing (e.g. birdbeaking, close to branched vessels) Normal Anatomy Mitigating risk of re- interventions Severe comorbidities that preclude safe re- intervention Patients potentially lost during F/U Long remaining life expectancy (young pts) Resolve proximal seal failures Targeted sealing of acute type I endoleaks Targeted sealing of late type I endoleaks Augmented stability in migrated grafts How to Manage EVAR with EndoAnchors? Case image from Gandhi RT, Katzen BT Treating a Type 1A Endoleak Using EndoAnchors. Endovascular Today March 2012 23:26. 13

Performance Verified equivalence to the strength of a surgical anastomosis 1 Designed to provide radial support and resist neck dilatation Safety In >4,000 cases and >23,000 EndoAnchors implanted to- date, no confirmed graft damage or late anchor fracture 3 No anchor dislocation after successful implantation in aortic tissue 3 No unanticipated adverse device events in ANCHOR registry (N=319) 2 Benefits Customizable placement to target concerning anatomical areas and Type I endoleaks Steerable guide for precise and accurate placement Motorized controls for two-stage deployment with repositioning EndoAnchor Tailored Seal and Fixation 1 Melas N et al, J Vasc Surg 2012;55:1726-33 2 Jordan WD et al, J Vasc Surg 2014 Jul 31. pii: S0741- 5214(14)00929-X. doi: 10.1016/j.jvs.2014.04.063 3 Based on data on file at Aptus as of May 2015 No damage post 400M cycles, equivalent to 10 years in vivo Images courtesy of Aptus Endosystems, Inc. 14

Cross Bar 3 mm 1.0 mm 3.5 mm Heli-FX System: Applier + Guide + 10 EndoAnchors Images courtesy of Aptus Endosystems, Inc. 15

Aptus Heli-FX Thoracic EndoAnchor System Aptus Heli-FX EndoAnchor System 16Fr OD, 62cm working length 18Fr OD, 90cm working length Aptus Heli-FX Product Offerings Images courtesy of National Institute of Health and Aptus Endosystems, Inc. 16

EndoAnchor Deployment Animation 17

Over 570 Patients enrolled as of May 2015 Registry Principal Investigators Europe: Dr. Jean-Paul de Vries Chief of Vascular Surgery, St. Antonius Hospital US: Dr. William Jordan Chief of Vascular Surgery/Endovascular Therapy, Univ. of Alabama Registry Design Prospective, observational, international, multi-center, dual-arm Registry Treatment Arms Primary Up to 1000 pts, Prophylactic Revision Up to 1000 pts, Therapeutic Duration 5 Years Follow-up Per Standard of Care at each center & discretion of Investigator ANCHOR Registry Capturing Real-World Usage 18

ANCHOR in the Scientific Literature 19 5 papers published since 2014 Rationale of EndoAnchors in abdominal aortic aneurysms with short or angulated necks De Vries JP et al. J Cardiovasc Surg (Torino). 2014 Feb;55(1):103-7 Results of the ANCHOR prospective, multicenter registry of EndoAnchors for type Ia endoleaks and endograft migration in patients with challenging anatomy Jordan WD et al. J Vasc Surg. 2014 Oct;60(4):885-92.e2. Analysis of EndoAnchors for endovascular aneurysm repair by indications for use de Vries JP et al. J Vasc Surg. 2014 Dec;60(6):1460-7.e1 Outcome-based anatomic criteria for defining the hostile aortic neck Jordan WD et al. J Vasc Surg. 2015 Feb 28. pii: S0741- 5214(15)00065-8 Midterm Outcome of EndoAnchors for the Prevention of Endoleak and Stent-Graft Migration in Patients With Challenging Proximal Aortic Neck Anatomy Jordan WD et al. J Endovascular Therapy 2015; 22(2):163170

20 ANCHOR Shows High Prophylactic Use Indications for EndoAnchoring in Revision n=99 Indications for EndoAnchoring in Primary n=307 Jordan WD et al. J Vasc Surg. 2014;60:885-892

Complex AAA and complications have warranted EndoAnchor tailored seal and fixation with ALL major endografts Jordan WD et al. J Vasc Surg. 2014;60:885-892 ANCHOR Includes All Major Endografts Confirms EndoAnchoring need is independent of endograft design, dependent on anatomical challenges and post-implant disease progression 21

1 Based on Aptus data on file as of April-15 Excellent Safety No confirmed late EndoAnchor Fractures or Graft Damage in >23,000 anchors implanted to date Usage patterns consistent with ANCHOR In over 4,000 cases to-date, 71% in primary In majority of primary EVAR cases, EndoAnchors address concerns for late complications Consistency with ANCHOR Demonstrates registry reflects real-world use of EndoAnchors 22 ANCHOR Parallels Commercial Experience 1

(1) At most distal renal artery (2)10% diameter change over 10mm length (3)As determined by the investigator Proximal Neck Anatomical Characteristics (based on Corelab) Primary n=242* Revision n=77* Max Aneurysm Diameter [mm], mean (+ SD)56 + 1165 + 13 Neck Length [mm], mean (+ SD)17 + 1315 + 12 Necks 10mm Length, N (%)101 (41.7%)36 (46.5%) Necks 15mm Length, N (%) 141 (58.3%)47 (60.5%) Neck Diameter 1 [mm], mean (+ SD)26 + 429 + 5 Conical Necks 2, %41.7%46.5% Neck Thrombus 2mm37%21% Neck Calcium 2mm48%12% Hostile Neck 3 53%63% *Note: Corelab sample sizes is different from total patients in ANCHOR. Corelab for all patients is still in-process. All above data is per Corelab except the Hostile Neck line item which is investigator reported. Jordan WD et al. J Vasc Surg. 2014;60:885-892 23 High Ratio Hostile Neck Anatomy in ANCHOR

Percentage Short Necks by Study Infra-Renal Neck Length* ENGAGE (Endurant) GREAT 4 (C3 Excluder) ITER 2 (Excluder) OVATION 5 (Trivascular) FORWARD 6 (Nellix) ANCHOR 3 (EndoAnchor) 10mm2.2%1.5%N/A15.5%17%41.7% 15mm4.3%N/A9.5%N/A29%58.3% Mean Infra-Renal Neck Length 10mm0mm5mm15mm20mm25mm30mm ENGAGE 1 (Endurant) mean: 28mm 1.Pol RA et al. J Vasc Surg 2014;60:308-17 2.Pratesi C et al. J Vasc Surg 2014;59:52-7 3.Jordan WD et al. J Vasc Surg. 2014;60(4):885-92.e2 4.Verhoeven et al. Eur J Vasc Endovasc Surg. 2014 Aug;48(2):131-7 ITER 2 (Excluder) mean: 26mm ANCHOR 3 (EndoAnchor) mean: 16mm GREAT 4 (C3 Excluder) mean: 28mm OVATION 5 (Trivascular) mean: 23mm 5. Mehta M et al. J Vasc Surg 2014;59:65-73 6. Presentation by Dr. Andrew Holden at VEITHsymposium 2014 7.Stokmans RA et al. Eur J Vasc Endovasc Surg. 2012 Oct;44(4):369-75 8.Oderich GS et al. J Vasc Surg 2014;60:1420-8. *Cut-offs for neck length may be based on xx mm or

Midterm outcomes (14-month mean f/u) exceed expectations from standard EVAR Shorter necks did NOT have significantly poorer outcomes 27 Excellent Outcomes as Prophylaxis in ANCHOR, Despite Majority Hostile Neck Anatomy Jordan WD et al. J Endovascular Therapy 2015; 22(2):163170 Ruptures, migrations or open surgical conversions 0.0% (0/208) Freedom from AAA-related re-interventions96.2% (200/208) 1 Freedom from type Ia endoleaks per Corelab98.5% (128/130) 2 Freedom from AAA expansion (>5 mm) per Corelab 98.4% (122/124) 1.N = 1 related to proximal seal: endograft body collapse in area with no EndoAnchor penetration 2.N = 2 associated with significant thrombus/calcium and 4- 5mm length necks

Studies Median Follow-Up Type 1 Endoleaks in Hostile Necks Meta-analysis, Antoniou et al 1 12-Months 20/205* (9.8%) ANCHOR Registry 2 14.3-Months 2/178** ( 1.1% ) 1.Antoniou GA et al. A meta-analysis of outcomes of endovascular abdominal aortic aneurysm repair in patients with hostile and friendly neck anatomy. J Vasc Surg 2012 2.Podium presentation by W Jordan, Benefit of EndoAnchors in Endovascular Aneurysm Repair, 2014 Vascular Annual Meeting * Hostile neck criteria: neck length 60 degrees ** Hostile as determined by physician in Primary Arm 28 ANCHOR Results vs. Antoniou et al. Meta-Analysis Seal Durability in F/U Compares Favorably No EndoAnchor Related SAEs or Re-Interventions Reported To-Date

Late durability data exceeds expectations 2,3 Aptus has the highest sac regression among all EVAR IDEs at years 2 and 3 1 At year 3, 82% sacs regressed 1 High sac regression predictor for lower complications 4 Aptus IDE Study: Highest sac regression, shortest average neck length among all EVAR IDEs 1 Based on Aptus data on file as of January 2014 2 Mehta M et al. STAPLE-2: The Pivotal Study of the Aptus Endovascular AAA Repair System - 24-Months Results. Abstract presented at SVS 2012 3 Mehta M et al. J Vasc Surg 2014;60(2):275-285 4 Goncalves FB et al. Br J Surg. 2014 Jun;101(7):802-10 [a] No type I endoleak or EndoAnchor dislocation observed in migrations, no evidence of endograft movement relative to aortic wall STAPLE-2 Shows Promise to Prevent Failures 29 EndpointMedian 3.4 yr. Type 1 Endoleak0.0% (0/155) Graft Migration (>1cm)3.2% (5/155) [a] AAA Ruptures0.0% (0/155) EndoAnchor-related safety adverse events 0.0% (0/155)

Short, reverse taper proximal neck Intraoperative Type I post-implantation of Cook Zenith 6 EndoAnchors implanted - Type I endoleak resolved Images from article: Gandi RT and Katzen BT, Treating a Type Ia Endoleak Using EndoAnchors, Endovascular Today, March 2012 EndoAnchoring to Target Acute Type I Endoleak 30

3 year F/U showed migrated Talent with type Ia endoleak Endurant cuff and EndoAnchors implanted - endoleak resolved Images from article: de Vries JP et al, Use of Endostaples to Secure Migrated Endografts and Proximal Cuffs after Failed Endovascular Abdominal Aortic Aneurysm Repair, J Vasc Surg 2011; 54:1792-4. EndoAnchoring to Re-Establish Seal in Migration 31

30 -45 LAO 30 -45 RAO C-arm positioning critical for proper spacing, visualization & implantation Min 4 EndoAnchors recommended For prox neck dia. > 29mm, min 6 EndoAnchors recommended Strive for even spacing around neck circumference EndoAnchors should penetrate vessel wall Select positions lacking excessive thrombus/calcium Minimum 4 EndoAnchors Recommended Note: C-arm positions above show just one possible combination EndoAnchors# of C-arm positions Recommended angular offset 4 EndoAnchors2 ~ 90 6 EndoAnchors3 ~ 60 Tips for EndoAnchor implantation: 32

30 LAO 30 RAO 90 Lateral 33 C-Arm Positioning for 6 EndoAnchors Note: C-arm positions above show just one possible combination

Move C-Arm in 15-20 degree increments Identify leak channel and then create a suture line along wall. Circumferential anchoring before/after T1 EL treatment is recommended: address concerns of long-term neck morphology changes 34 C-Arm Positioning for T1 EL Treatment

Major EVAR studies highlight late durability limitations e.g. EVAR 1, ACE, DREAM Greater complications in more hostile proximal neck anatomies Proximal seal stability remains key EndoAnchors designed to bring long-term stability of surgical anastomosis to EVAR Favorable safety profile Maturing data supports hypothesis of prophylactic benefits Clinical experience shows EndoAnchoring addresses clear needs in EVAR & TEVAR Augment strength when concerns exist for late complications Target and treat acute and late type I endoleaks Conclusions 35

Appendix

Challenges in Treating Urgent Aneurysm Patients 37 Limited options FEVAR lead times too excessive CHIMPs outcomes not definitive May be unfit for open repair Logistical difficulties Fast treatment needed to stop bleeding in rAAA Time constraints often preclude proper case planning and graft sizing Complex cases Anatomical challenges: typically hostile anatomy with short or angulated infrarenal necks and durability risks Type I endoleaks: can be lethal, highly critical to prevent onset or treat Types of patients receiving urgent treatment: Ruptured AAA Symptomatic AAA Rapid AAA expansion Large AAA diameter Types of patients receiving urgent treatment: Ruptured AAA Symptomatic AAA Rapid AAA expansion Large AAA diameter Images courtesy of Nic Nelken MD, Kaiser Hawaii and ANCHOR investigators 6.5cm diameter AAA Ruptured AAA

Need for immediate effective treatment vs. inter-facility transfer 16% rAAA patients transferred to another facility die before receiving AAA repair 1 Early benefits realized with EVAR vs. open repair in rAAA 2 Lower 30-day mortality (24% vs. 40%) Lower early major complications (58% vs. 76%) However, durability after EVAR remains problematic 3 Substantially higher late re-interventions after EVAR 25.8% vs. 4.7% for open repair Endoleak highest cause of post-EVAR re-interventions Constitute 43.8% of re-interventions Whereas no endoleaks after open repair Challenges in Treating Urgent Aneurysm Patients 38 1.Abstract presentation by Mell MW and colleagues of Stanford University at the 28 th Annual WVS Meeting 2.von Meijenfeldt GC et al. Eu J Vasc Endovasc Surg. 2014 May;47(5):479-86 3.Rollins KE et al. Br J Surg. 2014 Feb;101(3):225-31.

Rapid, high sealing performance in complex anatomy (N=39) 15 minutes average EndoAnchoring time with 100% implantation success 92% freedom from endoleaks at final angio despite >90% hostile proximal necks Durability maintained in follow-up 0% ruptures, 0% rebleeds, 0% proximal seal re-interventions (14 month mean clinical f/u) 0% Type Ia endoleaks per Corelab (3 month mean imaging f/u) Comparison with historical data shows EndoAnchors may reduce late type I endoleak risk Substantially lower rates in ANCHOR vs. comparable studies in standard EVAR Outcomes after Treating Urgent AAA 1 39 1 Based on abstract presentation at VIVA 2014 late breaking trials session by Dr. Peter Schneider: EndoAnchors in Urgent Endovascular Aneurysm Repair: Results from the ANCHOR Global Registry EndoAnchors shown as a useful adjunct to optimize seal and address concerns for re-bleed or initial rupture

aptus heli-fx overview physician slide deck developed by aptus endosystems, inc. mma05141501

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