2Recent Product Launches Volcano StoryIP and Core TechnologiesRecent Product LaunchesLatest AcquisitionsInitial venture funding in February2001CardioSpectraOCT catheter2007Cleveland Clinic VH2002NovelisForward Looking IVUS2008Jomed2003S5/S5iVH™ IVUSAxsunLaser OCT2008Philips(Rotational IVUS IP)2004Revolution catheterFFRPrimeWirePut technology together to address bigger market need – started with VP focus and licenesed and co-develop Virtual Histology with CCF, 2) acquired rotational visualization technology from Philips, 3) hardware and catheter technology and installed base from Jomed…Jomed was a $40 million revenue run rate company when we aquiredSo we now have a broad technology base of transducer technology, catheters, software for tissue characterization and navigation/mapping, and hardwareInstalled base of 3,700 systems in IVUS and FM and sales channel to leverageCurrent family of productsall introduced in last 2 years
3Advanced Technology Lab Volcano EuropeBrussels, BelgiumAdvanced Technology LabCleveland, OHManufacturing HeadquartersRancho Cordova, CAVolcano MAAndover, MAVolcano Japan Tokyo, JapanVolcano China,Hong Kong, ChinaVolcano Global SalesAtlanta, GACorporate HeadquartersSan Diego, CAAs I mentioned on the last slide, we have a very aggressive R&D investment taking place at numerous offices worldwide, including San Diego, Sacramento, Andover Mass., San Antonio and on the campus of the Cleveland Clinic.Our global reach includes more than 1000 employees, most of which operate in R&D, Manufacturing and Sales Support or Education.Volcano has more than 100 U.S. Account Managers and Clinical Consultants whose primary responsibility is staff training and proficiency on our multi-modality systems. Making IVUS and FFR as fast and as easy as possible for your team is the key to our success, and I am personally responsible for making that happen.Volcano OCT DivisionSan Antonio, TX
4Volcano TodayPlatform technologies for improving endovascular procedures200+ global patents in IVUS, VH, FM, FL.IVUS and OCTTechnology actor in interventional cardiology diagnosticRecent clinical studies: FAME and PROSPECT reinforce the use of FFR and IVUS (VH) to improve PCI’s outcomeNumerous additional large market opportunitiesOver 100 R&D engineers and scientists dedicated to new and existing technologyResearch Facilities in San Diego, Sacramento, Andover, San Antonio, ClevelandEstablished global business with a track record of successOver 3,700 installed systems worldwide (>50% of hospitals with cath labs)“This slide will provide a little background as where we are today. We feel that Volcano is the industry leader when it comes to IVUS, given the new product launches that we have initiated in the past few years, and the further investment in R&D and clinical studies that we have committed to in the years to come.”“We currently have more than 200 global patents in the specialties of IVUS, VH IVUS, FM and OCT”.“The company has grown from approximately $43 M in revenue in 2003 to 171 M, and 31% year over year. I believe we are the only cardiology company that has grown that quickly and consistently over the last five years.”“The growth has been fueled by two primary drivers. One has been the increased adoption of IVUS, where use in the US has increased from about 7% in 2003 to around 14% in This is still off from the approximately 67% penetration rate in Japan, but nonetheless, the technology has made some significant strides due to new product offerings, and concerns surrounding the clear limitations of angiography alone.”“The second driver has been our taking of market share from Boston Scientific. Estimates are that our portion of the U.S. market has grown from about 28% to 51% during that time, and we expect that surge to continue with the launch of our newest s5-Revo and s5-FFR here in 2009.”“It is easy to think of Boston as the larger company, but when it comes to IVUS, Volcano is the R&D powerhouse. We currently have more than 100 engineers focused on improving and innovating on our core technologies. We also have significant resources dedicated to OCT, ICE, Forward Looking IVUS, plaque progression studies and other therapeutic technologies.”“We have more than 3,700 IVUS and FM systems installed worldwide, and have an experienced management team dedicated to winning.”
5Volcano Platform Volcano s5: 5 modalities on 1system 2. IVUS and FFR Integration with all X-ray CompagniesCompatibility with GE, Philips, Siemens, Toshiba3. Coronary and Peripheral Applications4. Vision for the futureIVUS Guide Therapy, OCT, FL IVUS available soon on one multi-modality platform
6Volcano s5i Integrated Cath Labs s5i image onmain bank and in control room“To expound on this choice and flexibility a little more, here is an example of the s5i integrated into a GE Innova cath lab.”“The IVUS monitor display is placed on the existing monitor bank in the exam room, but can also be mounted bedside. Additionally, we provide video switching capability to display IVUS and FFR images on an existing color monitor. For the convenience of the staff, and for training purposes, a workstation is placed in the control room as well.”“Based on your desired workflow, a standard s5i controller and bedside monitor can be placed at the end of the patient table if that helps reduce procedure time.”“I should underscore here that there is only one CPU, and that all of the controllers are active simultaneously. You do not have to toggle between controllers as you do with the ilab.”IVUS and FFRPIM can hangfrom bed railFlexible, custom integration, through collaboration with cath lab vendors (GE, Philips, Siemens)s5i control devicescan be located atbedside and/orin control room
7IVUS/FFR integrated in every Cath lab type GEPhilipsToshiba“Volcano has taken care to seamlessly integrate the s5i into hospital X-ray systems. Our commitment to integration was evident at TCT, when Volcano IVUS was displayed alongside technology from every X-Ray company and several stent companies.”“In fact, Volcano is the ONLY IVUS company to document compatibility with all large X-ray manufacturers. We have written statements of compatibility with GE, Philips and Siemens, and verbal confirmation from Toshiba. This confirms that the s5i has a high video signal quality, DICOM compatibility, sufficient grounding, and no EMF interference when used in a GE, Philips, Siemens or Toshiba lab.”“To be very clear here, if you ask your Boston rep to provide you with a written document of conformability with any of these companies, they will not be able to provide that to you at this time, except for maybe GE through a press release.”“The effort that Volcano has made to solidify these compliance relationships was never more evident then at TCT last year, when our Volcano s5i was present and integrated into the booth x-ray systems of GE, Philips, Siemens and Toshiba.”Siemens
9Choice of 5 unique modalities Revolution™ high frequency rotational IVUSfor longer pullbacks and clinical study design
10Choice of 5 unique modalities Digital gray scale IVUS forfast, plug and play imaging
11Choice of 5 unique modalities ChromaFlo® stent apposition assessment to quickly confirm desired stent expansion and placement
12VH® IVUS tissue characterisation to identification Choice of 5 unique modalitiesVH® IVUS tissue characterisation to identificationof necrotic core
13Choice of 5 unique modalities PrimeWire™ FFR functionality for reliable identification of ischemic lesions as seen in FAME
14Leadership through Vision SOLID STATEIVUSROTATIONALIVUSFL.IVUSTherapy1H 2011FFROCT2H 2010Although we have clearly made the first step toward offering a true, multi-modality platform, by no means have we achieved our goals.Through a series of development efforts and acquisitions, we have positioned ourselves with a very clear path to add subsequent imaging and therapeutic technologies to our s5 platform, allowing Volcano to enter and develop new markets, and allowing you to leverage these technologies to improve the level of patient care your hospital can offer.These technologies include OCT (Optical Coherence Tomography), Image Guided therapy balloons, Forward Looking IVUS, Forward looking therapies, compatibility with ICE & TEE probes, and eventually image guided stenting.And the unique imaging component is only part of the benefit of this product line. The true potential is having a single platform, a single user interface and a single procedural workflow to ensure the entire staff can quickly and accurately use all of these different tools in the same predictable manner.This concept has been amazingly well received by our customers, and we feel Volcano will be an anchor point for the true cath lab of the future.Pioneer/MedtronicIGTFL.IVUS1H 2010IGT Balloon1H 20102011 Product Introductions2010 Product Introductions14The development, release and timing of any features or functionality described for our products remains at the sole discretion of the company.
15IVUS Guided Therapy - VIBE Combined IVUS and BalloonIVUS Platform : Eagle Eye PlatinumBalloon semi- and non-compliant
16IVUS Guided Therapy - VIBE Assess the vessel morphology and pre-DILATE if necessary for stent preparationImaging the vessel lumen & wall structures (IVUS-VH) as an adjunct to conventional angiographic procedures for adequate geographic stent placementBalloon dilatation of a stenotic portion of a coronary artery or bypass graft stenosis for the purpose of improving myocardial perfusionBalloon dilatation of a stent after implantation
17Volcano OCT Optical Coherence Tomography “Although the overall use of an OCT system is more difficult than fast, simple phased array IVUS, the trade-off is amazingly detailed near-field resolution, in the micron range. Here you can clearly see a dissection in this animal model image, and even see the cubed nature of the stent strut. This can help make very detailed and accurate lumen measurements, assess full stent expansion and apposition, and see dissections very clearly.”OCT provides a super high resolution tool to guide;proper lumen sizingfull stent appositionoptimal stent expansion
18Stent with acute formation of white thrombus Volcano OCT Optical Coherence TomographyStent with acute formation of white thrombus“OCT has potential beyond IVUS as well due to the enhanced resolution of the images. In this case, you can see intraluminal white thrombus forming on these stent struts within minutes of implantation of this animal study. Because the thrombus is white, it does not absorb all of the infrared light, and you can see the definition on the far side as it attaches to the vessel wall. With red thrombus, you would likely only see the closest thrombus border to the catheter, and shadowing behind it.”“In the research to indentify vulnerable plaques and culprit lesions, the micron resolution range is well below the post-mortem 65 micron definition of ‘thin-cap fibroatheroma’, adding another potential level of specificity to Vulnerable plaque assessment tools and trials.”OCT can provide a super high resolution tool to identify;Intraluminal thrombusThin cap fibroatheromas (10-15 micron resolution)Other?
19Volcano OCT Optical Coherence Tomography Proposed Volcano OCT ComponentsSuper-fast Spectral Domain imaging catheterDoes not require balloon occlusion for blood clearanceSimilar to rotational IVUS design10-15 micron axial resolutionBedside user controlsThe same user interface controls IVUS and FFRImage on existing monitor bank‘Volcano’s OCT technology is very similar to a rotational IVUS catheter. Instead of sending sound waves out as in ultrasound, it uses infrared light. There is a light fiber traveling down the core of the rotational drive cable, which is in turn hooked up to a rotational patient interface module which rotates the fiber inside the body. Here is Volcano’s revolution rotational IVUS catheters, which has a very similar distal design to our first generation OCT catheter.”“Now because OCT transmits in infrared light, red blood cells absorb that light, making penetration through blood impossible. In order to image the surrounding tissue, there must be a mechanism in place to usher blood out of the way of the imaging window via a contrast / saline flush. First generation OCT products required balloon occlusion of the proximal vessel to do this, but our Volcano OCT system is fast enough to allow imaging during a routine angiographic injection, removing the need for balloon occlusion.”Note: The Lightlabs M2 system (requiring balloon occlusion) is approved in Europe and Japan, but not in the U.S. Testing has begun on the M4 which is the next generation system. It is unclear at this point if the M2 will ever be approved in the U.S. or if they will skip directly to the M4. Although the regulatory path is still very unclear here in the U.S., we should expect a launch timing of around TCT of 2009 for a system from Lightlabs but there is a lot of uncertainty remaining.The development, release and timing of any features or functionality described for our products remains at the sole discretion of the company.
212 mm ahead of catheter tip 5 mm ahead of catheter tip Forward Looking IVUSPreView™Catheter-based1.5 mm imaging offset from tip45 degree off-set forward looking cone5 mm forwardImagine a funnel centred at your eye and looking forwardMackinaw™Same imagePulsed RF energy delivered to ‘red’ targetSteering is enabled by rotating the catheter and moving the targetAblation Region2 mm ahead of catheter tipIntimaVessel LumenMediaAdventitia5 mm ahead of catheter tip“To elaborate on the two catheter designs, the PreView catheter is simply a guidance tool. You select your CTO wire of choice and navigate to the target. You then advance the PreView catheter over the wire and begin imaging at the target site. The forward looking conical image helps to identify where the tip of the wire is, and more importantly, where the edge of the vessel is. This allows you to advance your guidewire through the CTO, and monitor your location relative to the vessel wall to ensure you don’t risk perforation.”“The Mackinaw is an active design, similar to the PreView but with on board RF ablation. Now instead of advancing with your guidewire, you use short, controlled pulses of RF to facilitate catheter advancement, again monitoring your location relative to the vessel wall real-time throughout the procedure. This allows you to tunnel your way through the occlusion, but maintain visual contact the entire time. Truly an eyeball at the end of your catheter.”New Ultrasound Lines
22Volcano FL.IVUS Forward Looking IVUS to facilitate CTO crossing CTOs indicationSuccessful product requires 3 attributesVisualization, Steering, DissectionDesign ConsiderationsCompatible with CTO guidewire of choiceAbility to visualize at 45 degrees when catheter approaches vessel wallPassive version for visualization onlyPreview™Active version equipped with RF ablationMackinaw™“CTOs are very prevalent in everyday clinical practice. It is estimated that between 10 and 15% of PCI procedures include an attempt to cross a CTO, 30% of these crossings fail. The alternative as you know is bypass, which is very expensive, with a difficult recovery. What if we could provide a device that allowed you to cross these difficult lesions in a targeted, image guided fashion?”“There have been a number of unsuccessful CTO devices in the past. Volcano’s platform is different because we have all three key attributes; visualization, steering and dissection capabilities.”“Volcano’s first two forward looking IVUS technologies are called the PreView™ and Mackinaw™. These technologies are still in the development phase and are not commercially available. The devices have an ultrasound transducer located at the end of the catheter, about 1.5 mm from the distal tip. The ultrasound device looks forward between 30 and 45 degrees, to create a ‘cone’ shaped image of the plaque ahead.”These Volcano Products are not currently available for sale. This document implies no guarantee as to future delivery or timing of these programs, and is meant only to highlight Volcano’s recent research & development efforts
23FAME study: FFR vs. Angiography for Multivessel Evaluation Demonstrated in 1,005 patients receiving DES for multi-vessel disease that FFR-guided PCIs resulted in lower MACE rates than angio-guided PCIsA gap in MACE rates was evident within 30 daysFFR guidance used during the PCI procedureshifted the survival curve upwardresulted in superior clinical outcomes Vs AngioFFR guidance improves clinical outcomes in patients receiving DES for multi-vessel diseaseFFR cost effective Vs Angio guided PCI2 Years FUFFR has the potential to identify the ischemic lesions that benefit from interventional treatment.Any stent placed in a lesion that is not ischemic rather increases the risk than the benefit for the longterm outcome.A significant reduction of MACE is obvious particularly within the first 30 days. This confirms the additional risk of stents that are related to mechanical matters due to sub-optimal implantation techniques. The impact on outcome is then maintained.The concept “Functionally complete Revascularisation, i.e. stenting of ischemic lesions and medical treatment for non ischemic ones” is confirmed by the long term benefit in outcome for those patients, who’s treatment strategy was guided by functional assessment (FFR).As less stents are implanted once only the ischemic lesions are stented the reduced number of stents and the associated cost have also a cost saving effect in addition to the improved outcome.
243-vessel imaging post PCI The PROSPECT Trial: A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable Plaque3-vessel imaging post PCICulprit artery, followed bynon-culprit arteriesAngiography (QCA of entire coronary tree)IVUSVirtual histologyPalpography (n=~350)Proximal 6-8 cm of each coronary arteryPROSPECT is a Multicenter Natural History Study using Multi Modality Imaging to assess ACS patients conducted in the US and in Europe.Patients could only be enrolled if the culprit lesion was treated successfully and without complications. The culprit lesion was treated under angiographic control only.Per protocol 3 vessel imaging was performed in the prox 6-8cm of the culprit and non culprit vessels using IVUS, VH and palpography. (There was also a substudy on MSCT).Patients were treated with controlled Dual APT throughout one year. Clinical FU was performed at 1month, 6 month, 1,2 and up to 3-5 years.3-vessel imaging was repeated in case the patient returned with an event that required re-intervention.Meds recAspirinPlavix 1yrStatinRepeat biomarkers@ 30 days, 6 monthsMSCTSubstudyN=50-100F/U: 1 mo, 6 mo,1 yr, 2 yr,±3-5 yrsRepeat imagingin pts with events
25The PROSPECT Trial: A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable Plaque20% of pts with ACS successfully treated with stents and contemporary medical Rx develop MACE within 3 years, with adverse events equally attributable to recurrence at originally treated culprit lesions (treatment failure) and to previously untreated non culprit coronary segment12% of pts develop MACE from non culprit lesions during 3 years of follow-upThe combination of large plaque burden (IVUS) and a large necrotic core without a visible cap (VH- TCFA) identifies lesions which are at especially high risk for future adverse cardiovascular eventsThe key messages related to this slide are written there already.You may be prepared for the question why the sum of the events in the culprit, non culprit and indeterminate vessels (12.9%, 11.6%, 2.7%) do not match the 20.4% of “all”. This is due to the fact that one patient can have more than one lesion – in the culprit and in the non culprit vessel.Also related to the multi variant bar graph: to be kept in mind: 70% PB is the most important independent predictor – meaning the biggest independent risk can be assessed by GS IVUS only!And: all significant predictors are based on imaging – not on angio or clinical parameters.
26The PROSPECT Trial: A Natural History Study of Atherosclerosis Using Multimodality Intracoronary Imaging to Prospectively Identify Vulnerable PlaqueVH-TCFA (Thick Cap Fibrous Atheroma)andNon Culprit Lesion Related EventsPositive predictive value for future eventsPIT (Pathological Intimal Thickening)andNon Culprit Lesion Related EventsNegative predictive value for future eventsVH provides positive and negative predictors and therefore has the potential to differentiate lesions that are at risk for events from those that are stable. This is a feature that goes beyond the capabilities of GS IVUS and on the other hand confirms the hypothesis that were based on histopathology: plaque composition has an impact on vulnerability / plaque activity!You may be prepared for questions: what if a lesion has less that 4qmm MLA or more than 70% PB and is a PIT: these are “borderline” / gray zone conditions! And as you can see: as 70% PB itself is the most important positive independent predictor the plaque composition has a secondary role. However: in general one can say: the presence of a TCFA is associated with an increased risk, the presence of a PIT confirms stability.
27Summary Volcano multimodalities in one platform Five options in one system… available today!DICOM / Worklist CompatibleBoth DICOM store and WorklistEndorsement by cath lab manufacturesLetters of compatibility with GE, Philips, SiemensCoronary ApplicationsFull line of catheters for diagnosis and therapy guidanceVision for the futureTrack record of success, clear plan for the futureMake Volcano ‘essential’ to every cath labOur Vision is to make IVUS, FFR, VIBE, OCT, FL.IVUS, etc.all available through the same user interface and workflow
28Angio alone is not enough Volcano provides the two pivotaltechnologies that clearly improve PCI:IVUS/VH and FFRVolcano provides diagnostic solutions to optimise the treatment of stable, unstable and AMI patientsVolcano future OCT, FL IVUS, VIBE options will continue to improve PCI’s outcome.
29Angio alone is not enough Right Patient, right lesion, right way!