Boston Scientific Corporation (BSX) Earnings Call Transcript & Summary

Good day, and welcome to the Boston Scientific Update at TCT Conference Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Susie Lisa, Vice President of Investor Relations. Please go ahead.

Thank you very much, and thank you, everyone, for joining us for the TCT 2020 Investor Update. I am very pleased to have with us this morning leaders from our Peripheral Interventions and Interventional Cardiology team. We'll kick things off with PI with Jeff Mirviss, our Executive Vice President and President of Peripheral Interventions; and then Dr. Michael Jaff, our Chief Medical Officer and VP of Clinical Affairs, Innovation and Technology for PI. Then we'll follow with Joe Fitzgerald, our Executive Vice President and President of Interventional Cardiology; and Dr. Ian Meredith, our Executive Vice President and Global Chief Medical Officer. Before we begin, the usual safe harbors apply. We will be making forward-looking statements, and we urge you to consult the risk factors of our latest SEC filings. So with that, we'll jump right into it. Jeff, please take us away.

Great. Thanks, Susie. Hello, everyone. It's a pleasure to be with you. If you can go to the first slide, great. Wonderful to talk to you just a little bit about the peripheral market, which we see as still a very attractive and growing segment at Boston Scientific and PI. We're focused on and we serve these very large and underpenetrated and, frankly, underdiagnosed disease states. And we see tons of room for us to continue to innovate to meet the patient unmet needs. And I think as you've seen over the past 8 months, this market is really a resilient marketplace and patients are continuing to benefit from a myriad of innovations across the disease states we're focused on. What you can see here on this slide is 3 primary markets in arterial, growing mid-single digits, where we're the category leader with a whole host of technologies to support patients with arterial diseases; venous disease, growing upper single digits and an expanded portfolio with BTG across pulmonary embolism, deep venous disease as well as superficial disease. We have the broadest portfolio in this strongly growing market; and then finally, in Interventional Oncology, Also growing upper single digits. We now have a broad category-leading portfolio to support the interventional radiologists in the treatment of patients with a multitude of various cancers. If you can go to the next slide, let me just give a quick update on the BTG acquisition. We've also been very pleased with how resilient the BTG portfolio has been, including during this pandemic. And we've realized some very exciting milestones, both from a product standpoint, with launches and geographic expansion, but also with regards to synergy capture, and we expect to continue to grow this BTG portfolio in the double-digit range. So we're feeling very confident about this portfolio. The portfolio is highly complementary. When you look at the Interventional Oncology portfolio, we now have a full complement of access and delivery tools and then all of the treatments for cancer, both in liver disease, in kidney cancer and other cancers. And same story on the venous side, where we now have a broad portfolio to help patients with pulmonary embolism and DVTs. And these segments are higher growth adjacencies. So we're seeing that play out in a broader commercial footprint now, both in the U.S., where we fully integrated the sales force and have a very strong commercial engine, as well as globally, where we brought some of these technologies to countries around the world, especially in the emerging markets. And so we've picked the low-hanging fruit in terms of a number of countries to expand into. And then we have made good progress on our medium and long-term plans to bring some of the BTG products to Asian countries, especially in China and Japan. So continuing to make progress from a geographic expansion standpoint. And then finally, from a synergy point of view. When we announced the deal, we had communicated a total of $175 million in synergies. And we're now communicating to you that all of those $175 million in synergies will come from cost. And we've made faster progress than our plans in achieving those cost synergies. And by the end of this year, we will be on a $125 million run rate. So achieving those cost synergies a bit faster than we had planned. So all in all, feeling very positive about where we're at in terms of BTG. On the next slide, I just want to touch on our portfolio because I mentioned the fact that these are high-growth markets in peripheral and we have a very strong pipeline to achieve that growth in the marketplace. And all of the products that you see on this slide are adjacencies to the peripheral portfolio, where we don't compete today. So we're excited about the fact that we're going to enter some of these new spaces. And I'll just touch on a couple of them. In Interventional Oncology, we're just launching now a new microcatheter called the TruSelect. It's a new segment for us, and the product is performing extremely well. So we're just now launching it in many countries around the world and we anticipate getting into the microwave ablation market. We have RF ablation and cryoablation. We will now add a third ablation modality for patients with liver cancer and other solid tumors, and we will be launching a microwave product in the near future. On the venous side, we have a new IVUS catheter that we will be launching as well as a new product to be used in conjunction with AngioJet called the Clothunter. And we're very excited about this product to be able to treat more clot than either AngioJet or EKOS alone. So another complement in the faster-growing venous space. And then finally, in arterial, probably the highlight will be the Ranger DCB, which we still anticipate launching in 2020 in the United States, as well as the new Athletis PTA Balloon, which is a high-pressure product in an area where we don't compete. We are the balloons market leader today, but we don't compete in this segment. So we're really excited to be able to enter a new balloon segment. And then finally, in 2022, we'll be looking forward to the launch of the only drug-eluting stent for BTK lesions, the SAVAL DES. So a great complement of solutions here to help our customers treat more patients, and again, all of which are new adjacencies to the peripheral space. So with that, let me turn it over to my partner, Dr. Michael Jaff.

Thank you, Jeff. Thanks, Susie. Good afternoon, everyone. Great to be with you. A couple of points on this slide to emphasize is the importance of our drug elution portfolio, as Jeff just mentioned. Obviously, we've got the most effective drug-eluting stent, the Eluvia stent that is based on the Lancet published IMPERIAL study, the head-to-head trial against Zilver PTX, designed to show non-inferiority, which actually showed superiority and continue to show statistically significant improvement in clinically driven target lesion revascularization at 2 years. So we're excited about Eluvia, and I'll have a little more to say about that in a few minutes. Obviously, Jeff just mentioned the next-generation Ranger drug-coated balloon. We're excited about this for several reasons. First and foremost, it's built on the most effective balloon catheter there is, the Sterling Balloon. It's a very low dose of paclitaxel with a unique surface coating. And the data about downstream particulates shows very low particulate rates, markedly lower than drug-coated balloons on the market. And then finally, as Jeff mentioned, SAVAL, that trial, despite COVID, has resumed quite effectively and we're over 80% enrolled in SAVAL. This is going to be a very important additional therapy for these most disadvantaged patients with critical limb ischemia. But it's worth me mentioning that the debate around paclitaxel in all-cause mortality has really changed over the past 6 months, and that's likely due to the combined work between all of industry, the Food and Drug Administration and, in fact, real-world evidence of large registries that are showing a complete lack of a signal of a safety disadvantage of paclitaxel in all-cause mortality. That includes a large Medicare database and an Optum database. So we're excited about this, and we have actually seen recovery in the market for Eluvia over the course of the past several months. And we really do believe that we are uniquely positioned, given the fact that we will be the only company that's got 2 solutions for patients with peripheral artery disease. We also have a large study called the EMINENT trial, which is a randomized trial of Eluvia versus bare metal stents. That trial is large and we'll look forward to those results. If we can go to the next slide, please. I do want to cover 2 important developments that have a significant impact on hospitals and health systems, particularly during this COVID environment where health care systems are struggling financially to recoup losses and regain their positions in the market. Just since October 1, there's been an NTAP or an additional coverage payment rule by Medicare for Eluvia. That was for inpatient procedures that adds an additional $3,500 or more onto the existing base DRG payment for stenting in the superficial femoral artery. The good news about this is that, that only happens for 3 components being met: one, the newness and uniqueness of the therapy, the device itself, the cost and the demonstration of some -- substantial clinical improvement, which I've just mentioned, clearly, has been persistent out through 2 years. This is specific to Eluvia, not applicable to competitive products. So we're very excited about this opportunity to get this out to the market for patients who could use this. The base DRG typically pays between $11,600 and $21,000. So the additional $3,500 is real. And then the second one we're very excited about is an additional reimbursement increase for EKOS. EKOS, of course, is the ultrasound-assisted thrombolysis catheter, an on-label device for pulmonary embolus and for peripheral vascular thromboembolic disease. And again, in October 1, 2020, there was an additional reimbursement released by CMS for inpatients, a 151% increased payment for EKOS procedures for pulmonary embolus and a more than doubling reimbursement for patients using EKOS in the peripheral vasculature. We're excited about this because this is the most studied technology for intervention in the pulmonary embolus space with 3 registries, clinical trials ULTIMA, SEATTLE II and OPTALYZE; the KNOCOUT registry completed, which included 1,500 patients; and because of our commitment to doing clinically meaningful clinical trials like IMPERIAL, like the COMPARE trial comparing Ranger to the Medtronic IN.PACT balloon showing equivalence with half the dose on that. We are also looking to impacting clinical practice with EKOS in pulmonary embolism. We look forward to further discussions down the road. And with that, I will turn it over now to Joe Fitzgerald. Thank you.

Thanks, Dr. Jaff. Great job. So for those of you who are wondering, no, you did not just joined the Rhythm Management call. I took over leadership for the Interventional Cardiology group 4 or 5 months ago. And I can tell you, I'm absolutely thrilled to be joining and leading the thousands of people that really execute globally across R&D, commercial, all functions. It's just a fantastic group, and I'm thrilled to join them. One of the things that I really like about the Interventional Cardiology group is really the scale, the breadth and the depth of our portfolio. And when I think about this, I was involved a bit 12 years ago when I joined the cardiovascular management team at a time when we had probably greater than 70% of our global revenue tied to the DES category. And today, when I look at a very balanced business across Interventional Cardiology, that rounds to about 1/3 in DES, 1/3 in complex PCI interventions and 1/3 in Structural Heart. I'm really impressed by the diversification and the multiple growth opportunities that exist in each of those areas. And I also -- I'm pretty darn proud of the team, despite COVID and the impact that we saw in Q2. I really like the commitment to the patient and the commitment to the customer. Here in Q3, we've executed across 8 global launches in our coronary therapies, PCI realm. We've initiated the global FLX launch. It was already in Europe, and we got off the ground to a very fast start in WATCHMAN. I'll talk about that with WATCHMAN FLX later. And then, of course, in our Structural Heart Valves group, continuing our LOTUS Edge launch in U.S. and Japan and getting neo2 launched and through our LMR in Europe. So I'm really, really excited about our ability to do this, despite the challenges with COVID around the globe. So now let's first turn -- I'm going to go a little bit deeper in our Coronary Therapies group. And to kind of understand our strategy and our pillars here, we kind of think about this business in 3 pillars. First is PCI guidance, how do we enable physicians to see and diagnose what is going on with the coronary disease within a patient. The second is what we call prepare, and that's all about calcium solutions that will enable the third category, which is treat, how do we deliver drug-eluting therapies, stents, drug-coated balloon therapy to that diseased vessel. So I really like the way and the offense. We have multiple launches in these categories. I won't drain all of them. But first, when we think about our PCI guidance, we've got 3 launches in multiple parts of the world. Our COMET II next-generation FFR guidewire, our first-generation of our new imaging platform, AVVIGO. You'll hear much more about that in terms of guidance system. That will touch FFR first. And then we'll expand across IVUS as well. And then the launch of our OPTICROSS high-density coronary imaging catheter. In the middle, in the area of calcium solutions, preparing the vessel for treatment. We're in the midst of our ROTAPRO launch. We have WOLVERINE cutting balloon launching globally. And then next year, we'll introduce our ROTAWIRE Drive. And then what I think is a really good point to make about our stent and drug-eluting therapies is we have continued to iterate on the SYNERGY platform. So right now, as an example, we're in the middle of early stages of launch of SYNERGY XD and SYNERGY with 48-millimeter lengths in both U.S. and Japan. We're in a limited market release for our first purposeful large vessel MEGATRON SYNERGY stent in Europe, and we expect that to come to the U.S. and other markets in early '21. We've got the actual AGENT drug-coated balloons study. The clinical trials begun in China and Japan, and we expect to have that IDE with first patient in the first half of '21. So really, really excited about this diversification. I think we said last year in 2019 was the year that we sort of did more than 51% to the stuff that's in the guidance in calcium solutions categories. So we are even less reliant upon DES and DES ASP erosion. So that's been a good mix shift for us in terms of diversifying our PCI, Interventional Cardiology, Coronary Therapies business. So with that, why don't I go next to our Valves and -- our Structural Heart Valves franchise. Obviously, we are continuing our strategy of pursuing a dual valve footprint globally. We're driving penetration and expansion of SENTINEL. And as you've seen in Q3, we just got our LMR for ACURATE neo2 started in Europe. A couple of other details on these 3 sort of pillars. We're really pleased with our SENTINEL progress. We have now penetrated greater than 20% of all U.S. TAVR cases and we've initiated our Protected TAVR study, which is a 3,000-patient 1:1 randomization against unprotected TAVR. And despite the COVID impact that we saw to all things clinical trials, we're currently enrolling at 20 sites globally and growing that footprint pretty quickly. Now turning to LOTUS Edge. I'm proud to report that we have opened more than 150 accounts in the United States. We are just starting to wrap up our limited market release in Japan with LOTUS Edge. And we, I think, are -- not I think, I know we are accelerating our momentum in our REPRISE IV medium-risk indication trial, which, like all of our other IDEs and clinical studies, did take a bit of a hit there in Q2 and the early parts of Q3. And as I already mentioned, we're thrilled to have ACURATE neo2 launching in Europe. That LMR is doing exceedingly well. And I think my key takeaways -- Ian, Dr. Meredith, will talk about this in a second. But the early feedback is exactly what we experienced in our [ CE ] approval study and that is improved ease of use, excellent gradients, lower pacemaker rates and improved coronary access. And we've seen that as we've started the early phase of the LMR and we have a pretty aggressive plan to get very deep into our ACURATE neo -- conversion to neo2 in Europe throughout the rest of the year. So with that, let me turn it to Dr. Meredith, who will talk about SCOPE II, additional highlights of neo2 and other parts of our Structural Heart Valve strategy.

Thanks, Joe, and thank you, everyone. As you all heard earlier today, the ISR-initiated SCOPE II trial comparing the original ACURATE neo valve with the CoreValve Evolut R or PRO system was presented. As a reminder, this is the first-generation ACURATE neo device, not the neo2 device that Joe just mentioned that we're launching in Europe or is under investigation as part of the U.S. IDE. Now the primary endpoint of the SCOPE II trial was a composite of all-cause death and all stroke at 1 year. And as you all know, the protocol specified that non-inferiority could only be claimed if non-inferiority was met in both the intention to treat and the per protocol analysis. Now as is shown here on the left-hand panels, we failed to demonstrate non-inferiority due to missing non-inferiority endpoint in the intention-to-treat analysis, although we met non-inferiority in the per protocol analysis. The point estimates and the absolute risk differences are shown here as well as the 95% upper confidence boundaries. And you can see the absolute risk difference in the intention-to-treat analysis was 1.8% with a 95% upper confidence boundary just marginally passing the 6% prespecified non-inferiority margin. And it was 1% for the per protocol analysis, and we can discuss those differences between the 2 designs later. While we were numerically better in disabling stroke and, in fact, all stroke, the main reason for missing the intention-to-treat endpoint was a slightly higher mortality due to cardiac mortality. The cardiac mortality differences are likely to be due to a higher rate of paravalvular leak here, nominated as aortic regurgitation. 96% of the aortic regurgitation seen in this study was paravalvular leak. And as you can see, there was a higher rate of paravalvular leak with the ACURATE neo platform, particularly moderate to severe paravalvular leak at 30 days, 9.5% versus 3%. Now PVL, we know, is associated with the increased risk of cardiac mortality, and this has been reported in multiple TAVI studies and meta analysis previously. While we're disappointed that we missed the endpoint and the PVL data, our next-generation neo2 data was specifically designed to minimize PVL and we'll talk a little more about that later. Can I have the next slide, please? There were several important positive findings in the SCOPE II trial, and I'd like to highlight the ACURATE neo's lower new pacemaker rate. And importantly, this is not a post-hoc analysis. This is a pre-specified secondary endpoint that was powered for superiority and it clearly showed that ACURATE neo has the lowest pacemaker rate amongst self-expanding valves. The rate was 10.5% versus 18% at 30 days, an 11-point -- 11% and 18% in 1 year. Now consistent with the much lower rate of pacemakers, we saw about a 30% lower rate of left bundle branch block. And left bundle branch block has been associated with an increased risk of mortality in longer term. So a significant reduction of that will certainly play out in the longer term. It's also important to note that physicians have been very pleased with the real-world experience of this first-generation ACURATE neo system, which has been used to treat more than 30,000 patients globally with really good outcomes. In fact, with patient-tailored therapy, patient-specific therapy, the ACURATE neo valve demonstrates very good clinical outcomes and low PVL rates in a number of real-world studies. Let's go to the next slide. Perhaps the most important thing here, though, is that it is important to recognize that as we do with all products, we continually improve these platforms with each new generation to improve the efficacy and the safety. The second-generation ACURATE neo2 system was actually developed primarily just to decrease the rate of PVL. And as you can see here, it has a 60% larger skirt -- outer sealing skirt, and this sealing skirt is much more effective in preventing paravalvular leak through the calcified interstices of the native valve. The end result is that the ACURATE neo2 system remains -- retains many of the benefits of the first-generation ACURATE neo, the procedural efficiency, best-in-class pacemaker rates, the single-digit gradients and a very effective, low -- large effective orifice areas. We heard the panel today talk about that. And easy coronary access. And adds to that now a far improved PVL. And we know the data for PVL is improved with ACURATE neo2 because the CE Mark study demonstrated a significant reduction in paravalvular leak in core lab adjudicated analysis, where we found the rate of moderately to severe paravalvular leak was in the order of 3% at 30 days and 2.5% at 1 year. Those numbers are completely in line with the third-generation valves that are currently available from competitors. Now with respect to the U.S. regulatory update. For the U.S. regulatory approval for neo2, we had originally hoped to leverage the first-generation data from SCOPE I and SCOPE II trials alongside the ACURATE IDE, which as we said, assesses the ACURATE neo2 platform. Now that we've seen the results of the SCOPE I and SCOPE II and learned more about the differentiated performance of the PVL rates, SCOPE -- ACURATE neo1 to ACURATE neo2, the data collected from the U.S. ACURATE neo IDE will become the primary pathway for our regulatory submission in the U.S. Therefore, while we're still in discussions with the FDA, we believe we will need to add more patients and a longer follow-up period, and thus, our original time lines will be extended. We are also taking the opportunity here to reset the timing expectations. We now estimate the FDA approval and U.S. commercialization of ACURATE neo2 to be 2024. Joe, I'll hand it back to you. Thanks.

Thanks, Ian. I think the other comment, too, because one of the things we've done here is, especially in a COVID recovery, we've looked at all of our clinical trials. And I had mentioned REPRISE IV where we're seeing good recovery in those patient accrual rates. But that trial as well, I should have mentioned earlier, that trial's expected timing for the intermediate risk timing has also now moved to '24. And I put a lot of effort on understanding both the neo2 timing, REPRISE IV indication timing. And I think this is a relevant sort of timing, and I just want to point that out on both of them. So now on this slide, let's talk -- we wanted to update sort of our WATCHMAN target addressable market. So what you'll notice on this slide is, in the past, I think the last time we showed this slide, we were talking about greater than a $1 billion market in the 2023 time frame. When we look at our momentum that we established in 2019, the success early in 2020 and the growth rates pre-COVID and the success of our both direct-to-patient and direct-to-referral activities as well as what PINNACLE FLX or a product like PINNACLE FLX brings to enlarging the patient population, we believe we can have an addressable market that is $1 billion higher than it was at the 2019 time frame out in 2024. And that's despite the fact that one of our studies, ASAP-TOO, which we have been conducting for multiple years, really started to have seen sequentially even despite COVID, without even considering COVID, a pretty large slowdown in the recruitment into ASAP-TOO for the purely contraindicated patient population. And physician feedback there has been patients really do not want to risk the chance of being relegated to the no treatment arm. So we've made the decision to discontinue enrollment in ASAP-TOO. There have been no safety events, no safety signals in this study. This is more about us now focusing longer term on 2 indication expansion study, one of which, OPTION, which is the ablation plus WATCHMAN or ablation without WATCHMAN and long-term anti-coagulation study, and the CHAMPION AF study that we talked about in January. We think those 2 studies will expand the indicated patients, bring in more lower bleeding risk patients and help enable a target addressable market in excess of $3 billion in the 2026 time frame when those trials wrap up. So again, just to repeat, we're focusing more now on CHAMPION AF and our OPTION studies, and we have decided to discontinue enrollment in the contraindicated ASAP-TOO studies. So we go on to the next slide. I want to spend time talking about our PINNACLE FLX performance and, more importantly, the early feedback here as we have begun commercialization in the United States. And just a reminder, we're in our second year of launch. So we've got quite a bit of experience from our European WATCHMAN FLX experience over the last year and 1 year and 9 months-ish. So just as a reminder, we presented the PINNACLE FLX data, outstanding efficacy, 100% LAA closure at 12 months, lowest ever reported safety events per -- procedural safety events and clearly demonstrated that we could treat a wider range of anatomies with our WATCHMAN FLX platform. After receiving approval in late July, we initiated immediately our limited market release at select centers. That went faster than expected. And we have now, late Q3, early here in October, we have commenced a full market release of WATCHMAN FLX in the United States. And I will tell you that all of the key KPIs, metrics that we are looking at, whether it be safety, ease of use, all similar to what we've learned in Europe and in the PINNACLE FLX study, physician demand, account contracting, pricing, physician training, all of our metrics are green and ahead of our expectations. So today, when we look at how we continue to penetrate and convert to FLX, we believe that nearly 75% of our WATCHMAN implants in the United States will be converted to WATCHMAN FLX by the end of December 2020. And as I look at 2021, I believe we'll have 100% of our accounts converted, and 100% of all of our implants will be WATCHMAN FLX by mid-'21. And sort of tied to the target addressable market, I want to just talk about one component, and there are multiple components of how we drive patient funnel. And I really want to give a shout out to our marketing and market development team because what we're doing here is really highly innovative stuff, and we're driving this patient funnel. I want to talk just briefly about our new commercial, which is really centered around restoring joy to life, launched about 30 days ago. And its real purpose is to highlight that WATCHMAN is a onetime therapy for life, whereas you contrast that with a lifetime of dealing with oral anti-coagulation. And just as a highlight, both this commercial and our previous commercial, really since 2019, we've actually communicated via this commercial with 90% of AFib-eligible patients greater than 8x per week. And we have metrics that we really like. For instance, how many of these patients that get exposed to it are driven to our patient questionnaire on our [ SPUR ] platform? And recently, I asked that question, we have 75,000 patients who have responded to the commercials and went on to take the patient survey. So all of that sort of leads into the how we drive the patient funnel and how we have achieved greater than 100,000 implants to date. So with that, I think we'll just put up and leave up during Q&A sort of our pipeline across both Peripheral Interventions, Coronary Therapies and Structural Heart when we think about the next 2-plus years. And then, Susie, I'll hand it back to you, so you can moderate Q&A.

Great. Thanks, Joe. And bear with us as we try this new format. I think first question, Ian, will go back to you. Question came in from a variety of places including Bob Hopkins of BofA, Larry Biegelsen at Wells Fargo and Vijay Kumar at Evercore ISI. Essentially, Ian, how do you think physicians are thinking about SCOPE II results, also with the SCOPE I results from last year? And then maybe, Joe, if we could pivot that to thoughts about potential implications for our European TAVR share. So Ian?

Yes. Thanks very much. And thanks for the question. I think it's a very good question. I think, really, the panel discussion summed it up the best. And Michael even made this comment. It is a first-generation device on one side of the ledger in this clinical trial versus a third-generation device on the other side of the trial arm. And he raised the hypothetical question, which I think was a really good one. Had this been a study of Sapien XT, their Edwards first generation, versus S3, their third-generation valve, would we have seen the same results? He thought, yes, you probably would. Had this been CoreValve versus Evolut PRO, first versus third, would we have likely seen the same results with respect to paravalvular leak? The answer is probably true. And in the half hour after the -- he made that statement, I've spoken to several investigators. And they felt the same way. They feel that the trial is a reflection of the difference in the paravalvular leak protection capabilities of first-generation valve versus a valve on the other side of the trial, in both SCOPE I and II, that had been multiple iterations along in improving the safety and efficacy and reducing the burden of PVL. I think in both studies, you can actually point to the difference if we lay aside some of the methodological differences in SCOPE II. But if we look at SCOPE I and SCOPE II holistically and you say, well, you could really pin much of this on the differences between a third-generation device with less paravalvular leak versus a first-generation device, ACURATE neo, with slightly more paravalvular leak. And we know that that's associated with the greater likelihood for more dilatation after the device is deployed. And we note that it's more likely to be associated with a long-term difference in cardiac mortality. So I think most physicians are putting this in perspective. Now there are some other stuff with nuances that we can come back to. But I think what they realized is if you use this valve in appropriately selected patients, ACURATE neo1 is achieving excellent results. And for the investigators in the U.S. ACURATE IDE with ACURATE neo2, they are very comfortable and happy with the results that they're seeing thus far. So I think they'll put this in perspective and look at this new generation versus older generation going head-to-head, you're seeing the time-related differences and evolution of the platforms.

Thanks, Ian. So Joe, then if you could comment on thoughts on potential implications for EU TAVR share. And then a related question from Robbie Marcus at JPMorgan. So what is the rationale or "pitch" for using ACURATE neo2? Where does it fit?

Okay. So when you look at our experience with ACURATE neo first gen, post-SCOPE I, yes, we lost a minor amount of share. So that was a headwind post-SCOPE I. I think we really have to point out, right? We are nearing full market launch or we'll get there by end of year for neo2 in Europe sometime around the end of the year or Q1. And I think we believe ACURATE neo2 is a share-gaining launch. And it's for the reasons that Ian and I already talked about: best-in-class PVL rates, best-in-class pacemaker rates, excellent gradients and excellent ease of use and coronary access. So I think we have to separate the ACURATE neo from the ACURATE neo2 because we know the data we've gotten out of the EU supportive clinical study, we see the response in the IDE for neo2. It's a different second-generation device. And I think that drives share gains as we expand our launch footprint in Europe.

Perhaps, Joe, I could add on to Robbie's question as to where do you see this fitting in. ACURATE neo2 is a supra-annular valve with vastly improved EOA and gradients and hemodynamics associated with it. So it is a direct comparator or competitor for any situation where you would use another supra-annular valve, say, Evolut R or PRO, but with a lower pacemaker rate. And then there are many who would use these valves routinely as their workhorse valves if they're easy to use. And so we think that ACURATE neo will have the ease of use, plus the advantage of the hemodynamics, plus the advantage of the lower pacemaker rate. So it will be wherever you use a supra-annular valve plus a more significant share of the workhorse group, simply because of the ease of use issue.

Great. All right. Thank you. Now to shift over to PI. Jeff, a question for you from Chris Pasquale of Guggenheim Partners. You mentioned $175 million in synergies, all from cost synergies. Now his question is, what was the original split, cost versus revenue? And is there an issue with the revenue synergies or more confidence in costs?

Okay. Yes. So the original communication was an 80-20 split, 80% cost, 20% revenue synergies to total $175 million. What we're communicating now is greater cost synergies and faster. So I mentioned we'll be on $125 million run rate by the end of this year. In addition to that, we still are believing that we will get revenue synergies. We're getting them now because of the bigger commercial engine, the category leadership across IO and venous as well as the geographic expansion where we've moved into many countries with the portfolio. And then we're, again, committing to what we believe will be double-digit growth for the BTG portfolio. So net-net, it's just a positive.

Great. Thank you. And then one for Dr. Jaff, I guess, related to the whole paclitaxel discussion. Just a question on sort of what you're seeing -- you touched on it a bit, but what you're seeing in the actual clinic? And then, Jeff, maybe you could comment, or Dr. Jaff, with respect to the NTAP, is that having an impact on what we're seeing with Eluvia? And then finally, Dr. Jaff, if you care to comment, any thoughts on the SUNSET pulmonary embolism trial and what that could mean for EKOS?

Thanks, Susie. I'll take a first stab and then turn it over to Jeff. We're seeing a significant uptick in Eluvia sales across the United States over the past several months. The discussion has become quite simple for clinicians to have with their patients. Previously, as you know, the FDA made it clear that they expected that there would be a shared decision-making. Well, that's what we, as doctors, do with patients every day. And given this added volume of literature showing no safety signal for hundreds of thousands of patients comparing paclitaxel-treated versus bare-treated patients, that discussion is much easier for patients, particularly when we don't want to have patients coming back to hospitals for fear of COVID because of TLR rates with Eluvia having the lowest TLR rates. Just a quick thing about SUNSET PE, and then I'll turn it over to Jeff. For those of you who don't know, SUNSET PE is a small 80-person randomized study sponsored by UPMC. This took a very long time to enroll. It's a randomization of an in-hole, side hole catheter for catheter-directed thrombolytic therapy versus EKOS catheter-directed thrombolytic therapy with ultrasound. The protocol, as I said, took a very long time to enroll. There were multiple changes to the protocol that actually caused sites to drop out from participating. The primary endpoint, frankly, has no meaning. It's a thrombus reduction by imaging endpoint. It's not a clinically meaningful endpoint. There's never been a study that suggested that a change in the appearance of thrombus on CT correlates with a clinically meaningful outcome. The duration that does matter for treatment of pulmonary embolism is 1-year long-term improvement in physical functioning, like the OPTALYZE long-term publication showed. And so an acute reduction in thrombus burden really does not answer a clinically meaningful question. We obviously have run trials that have clinical meaning, IMPERIAL and COMPARE, as I mentioned, and continue this strategy in the future. And of course, the EKOS reimbursement increase that I mentioned earlier helps with this debate as well. But Jeff, any other thoughts on that or Eluvia?

I think we lost Jeff. I should have mentioned -- thank you, Dr. Jaff. But the Eluvia question was from Mike Matson at Needham, and the SUNSET PE study was from Larry Biegelsen at Wells Fargo. Maybe we'll shift back to our IC group, if we could. And Joe, a question, again, from Larry Biegelsen at Wells Fargo. WATCHMAN FLX, is it helping drive utilization in existing accounts or expanding to new accounts? And then, Ian, for you, a question from Danielle Antalffy at SVB Leerink. Any comments on the IVL or CAD III coronary data this morning. Joe?

Yes. So on the FLX driving utilization, I'll refer us back to what we saw in the PINNACLE FLX actual clinical data, where greater than 6% of those patients were patients who were assessed and not able to be implanted with the original WATCHMAN. So the short answer there is, yes, we think this -- the introduction of FLX will open up a larger patient pool for larger, shallower appendages. We're convinced of that. I think it's less, Larry, about expanding to new accounts. What we've seen early in both the Europe launch and in the U.S. launch is that we have people who have not been -- whether it be interventionalists or EPs, who have not gotten into LAAC as an implanter yet raising their hands and saying, I'd like to be trained, I like the safety profile of the device, the ease of use, the application to a wider range of LAAC morphologies. So the answer to both is yes. But it's less about new accounts, and it's more about expanding the implanter base within -- in the large 600-plus large cardiovascular centers that we're already in. And then on -- I think, Susie, the second part of that was any thoughts on competition. We obviously monitor this with every piece of news that comes. We expect to see the data from Abbott with their Amulet device sometime in the first half of '21. And I think they've communicated that their commercialization, when approved, is in the second half of '21.

And also, Ian, before we go to you, Joe, just a question of clarification from Raj Denhoy at Jefferies. The intermediate risk approval time line for LOTUS Edge and the ACURATE neo2 in the U.S. and the ACURATE neo2 U.S. approval time lines are now both 2024, correct?

Yes, they are. They're both '24. And Raj, it's a good question. I mean, this is an area I've really focused on. I'm kind of a stickler for putting realistic plans and then hitting those plans. And you know that from my time at Rhythm. So the time frame is '24, and Ian and I and the clinical ops team have beat this up pretty well and both dates are 2024.

Great. Thanks. Ian, on IVL and any other clinical trial thoughts worth sharing?

Yes. So I think that -- thank you, Susie. I think that's a good question from Danielle. The -- as you saw, the CAD III trial for IVL was just presented by Dean Kereiakes, so I think the results were very good. We saw it meet both its safety endpoint and its efficacy endpoint and met a number of procedural metrics as well with good clinical results with respect to repeat revascularization. So Boston Scientific, we have been long believers, and Joe showed the slide before, in an appropriate visualization in complex coronary artery disease assessment of the burden of calcium and having appropriate tools to manage that. And we do have a range of options for managing calcium. So I think this was a good trial result for intravascular lithotripsy and supports the appropriate use of therapies to modify calcium to get the best long-term results in complex PCI.

Great. So another question from David Lewis at Morgan Stanley. Joe, can you comment on sort of where we are in terms of the LOTUS Edge rollout globally? And thoughts about expectations for share gains over the next few months.

Yes. So as I said earlier, let's start with U.S., we -- I consider that we just annualized our launch. COVID sat right in the middle of that first 12 months of launch. But I like what I see in terms of us being now in 150 accounts in the United States. I think our launch is -- I know our launch is gaining momentum. We've got an improved version of iSLEEVE that will hit the U.S. for an LMR in November. So we'll -- we think that will have sort of an improvement in the ease of use and the overall implant experience as well. We continue to iterate the LOTUS Edge implant techniques from learnings all over the globe. And I really like what I see Sam Conaway's team doing there. So we're going to continue this. This is now a ground game where we are expanding our footprint in the U.S. Each month, we're growing actual procedures per center, per month. And I probably don't want to give a point estimate, but we are going to continue to improve our ground game and then add on things like improved iSLEEVE and continue to make every implant and every next case better than the last case. And then the only other comment I'll make is we're very early in the Japan launch. That's been a very targeted LMR with a few sites in Japan that has just wrapped up, and now we are starting to plan for our market expansion in Japan. And that's -- I'll stop there, Susie.

Great. Thank you. And back to WATCHMAN. We mentioned the discontinuation of the ASAP-TOO study. And Ian -- or Joe, I wonder if you could comment on a pathway for reaching these patients with an absolute contradiction to oral anticoagulants. And that question is coming from Chris Pasquale again.

Well, perhaps I could start, and Joe, you could follow. I think the most important thing is that these patients are largely being treated today anyway. And that was the reason for discontinuing the study, was that it was extremely difficult to find patients to be randomized to the control arm. The awareness of the benefits of the therapy has meant they were reluctant to be randomized in this trial to the control drug treatment arm when there was the option of left atrial appendage closure with WATCHMAN available. So these patients are being treated. More importantly, as you know, we have the CHAMPION trial initiated and first site activated. So we expect the first patient to be enrolled fairly soon. And that trial will actually provide ultimately, because of increased bleeding risk populations in that, the approval for the absolute contraindicated patients. So Joe, if you've got any other comments you want to add to that?

No, you hit it on the head, Ian. Maybe, Susie, we've got 4 minutes left. Let's try to get to as many questions as possible.

Sure. So one for the PI team from Joanne Wuensch at Citi. How are you thinking about rolling out both Eluvia and Ranger? And which device is best for which patient? Jeff, if you could talk about that, please?

Yes. I think this has been part of our strategy all along, to be the company with all the tools in the toolbox, to be able to support our customers for what they feel is best for their patient. No other company really has the ability to do that. And what we're seeing start to pan out is patient and lesion complexity is pushing physicians to choose one device over another. And all along, we felt that the most simple lesions could be treated with a bare balloon or a bare stent. Moderate complexity patients or lesions could be perfect for a drug-coated balloon with or without atherectomy. And the more complex patients and lesions where Eluvia has really shined in the clinical data is perfect for sustained release Eluvia. Michael, anything to add to that?

All I would add is with our large ELEGANT registry starting next year, 5,000 patients international, adding a significant proportion of people who are not routinely studied in trials, underrepresented minorities. We're going to learn in geographies of the world, based on underlying comorbidities, what patients do better with what therapy, no one else would be able to do that, and will really contribute to the medical literature from that.

So I think one final question is from Rick Wise at Stifel, talking about one of our competitors signaling more head-to-head competition, clinical trials, et cetera. Any thoughts on any changes that you've seen in the marketplace or how we're positioned with respect to that? Essentially, a competitor yesterday signaling a more intense share gain mindset. Thanks for your comments, Jeff and Joe.

Yes. I'll just say, I haven't seen that in peripheral, but what I would say is we're the category leader in the spaces where we compete. As I showed, our pipeline is extremely robust. And we're going to continue to invest to bring new meaningful innovations to help patients supported by unparalleled clinical evidence. That's what we've been doing, and we're going to continue to do that going forward. Joe?

Yes. I think a lot of what we've seen in Structural Heart and DES, we see a lot of head-to-head comparisons just for approval. And it's always an option. I would say that especially in a -- what kind of studies that you could see in the LAAC space probably will follow the same path as what you've seen in the valve space with more head-to-head post-market studies. As an example, the first product to get approved in this country from a competitor will be from a -- will be compared against original WATCHMAN. And most of the U.S. and most of the world will have flipped to the next-generation WATCHMAN FLX. So I think it's very possible you could see more head-to-head in that space. Ian, do you want to comment on that?

No, I think you're right, Joe. And I'd just remind that the ACURATE IDE trial is indeed a head-to-head of new generation ACURATE neo2 versus commercially available Evolut R, PRO and S3. So I think there is a role for head-to-head in trials but with contemporary generations of technologies because when you have 2 different generations of technologies, it's hard to know how to ascribe any differences should they actually occur. But I think there is a definite role for head-to-head trials. And I think we'll see more and more real-world propensity matched comparisons and other forms of matching use in real world rather than just simply the traditional head-to-head randomized control trial because I think larger data sets in broader patient populations might be able to tease out real advantages for one technology over another or show no differences at all.

All right. Great. That brings us to the top of the hour. Jeff, Michael, Joe, Ian, thanks very much. And thanks, everyone, for dialing and calling in. Thanks.

Thank you.

Thanks for having us.

Thank you.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.