All right, so hi. I'm Matt Taylor, the U.S. Medical Supplies and Devices analyst here at Jefferies, and I'm pleased to be hosting David Hochman, who's the CEO of OBIO. They have a very interesting model that's sort of like a pharma partnership model they bring to MedTech. Exactly. With a couple of lead programs that we've outlined. We launched coverage on the stock a few months back with a buy rating, and I'm pretty excited about the BACKBEAT hypertension program and the opportunities with Terumo. With Virtue, yeah. Virtue with SAB, a very differentiated platform for delivering drugs. Yep. Almost like a drug-coated balloon, but not quite. Better. Better. We strongly believe better. And with opportunities for future partnerships. So I'm teeing you up there, but David, maybe you could talk a little bit about A, how you came up with this idea. Sure. Why you think it's the right time for MedTech, and some of the early proof points that you're seeing with the two lead programs? Love to. Thanks, Matt, and thanks, as always, to have the opportunity to chat and to be at the conference. I think, particularly given that the majority of content at this London meeting tends to be focused on biotech and new drug development, really that was the inspiration for our business model. It is expensive, difficult, risky, time-consuming to develop new therapies, whether you're doing that on the drug side or the device side. On the device side, most emerging growth companies that you might be in your coverage universe or that you're watching tend to be focused on driving value around a commercial asset that they're spending money building out, distribution, new sales force. While when that works, it can work really well, it's challenging. It's a different skill set than often the skill set it takes to develop new IP and bring something through clinical trials. And so our team's really focused on that capability. We're really good at developing technology, good at driving the data generation. And we felt, why couldn't we take the business model so often used to create and drive value in drug development, partnership between a smaller development-oriented company and a large established global commercial platform where they're sharing the risk and rewards associated with the new product candidate, often in the drug world, even as early as preclinical? But why couldn't we do that at late, pivotal stage in the MedTech space? So we formed Orchestra BioMed really to pursue that model. Obviously, had to engage shareholders. We've got some great shareholders, two lead institutional investors, our RTW and Perceptive that believed in that model, convinced we could make money through long-term revenue share that we would have with our partners. And so we've successfully partnered the two lead programs. What we think we're doing from an investor standpoint is making defined, hopefully, time and financial bets on technology that we think has been validated in the clinic. We have great data on both products. We're bringing that technology forward to have an impact on big established markets. Our partners are much better positioned to immediately take advantage of, let's say, approvable data and an approvable asset and get that to the large group of patients we can serve. We think it's a more capital-efficient model. We think it really focuses on inflection pointed data while answering key questions about execution and allows us to think long-term about diversifying the pipeline, the programs, taking full advantage of our technology, and solving another key issue that I think is what drove the partnerships we have. MedTech companies need to drive growth. You talked about it in your comments last night. We need to see differentiated organic growth. The difference between a company that's struggling at 4%-5% and a company that can deliver double-digit growth is a huge sea change in market value. The constraint for MedTech, though, is on R&D spend. The average R&D spend for a MedTech company in the industry is about 7%. There are outliers, and it does make a difference. So really what we think we're solving for our partners is giving them a long-term view of growth assets. The AVIM program, which we're partnering with Medtronic, could have a huge impact on a core Medtronic business, drive top-line growth, but really substantial margin contribution, and improve their competitive position while caring for their patients more effectively. They're planning around that long into the future without having to buy the asset. They're influencing and helping us execute the program, but we're spending the money on our P&L, and we're driving the work. So Medtronic's getting this efficiency, this growth planning without dilution of the P&L. And we have similar benefits to Terumo, our partner for Virtue. And we think that model, whether we do it or others begin to follow suit, has a big role to play in how we drive future innovation in MedTech. It can't all be done just waiting for something to become accretive. So those are, I think, the key drivers. We're learning a lot. You're still needing to figure out how to align interests, both from a deal standpoint, how do we make sure that we're protected from our value interests, that it makes sense from a margin perspective to pay a royalty for our partners. I think what's really exciting, and as I'm here in London at your conference, but also we have a number of sites opening for our BACKBEAT study. I spent the full day yesterday talking to physicians, the operational aspects of how we're really using this model, doing things that would be very difficult for us to do on our own, but also doing things that Medtronic, for example, in the BACKBEAT study, would have a hard time doing without an outside partner. It's exciting. We're liking how physicians and their teams doing research are reacting to the kind of real work, which is data generation. We're operationalizing this, and we're excited about where we can take it in the future. Maybe we could start by talking about the lead programs a little bit more. Sure. You mentioned BACKBEAT, which is a product for hypertension. Mm-hmm. On an existing pacemaker that can just be turned on. I'd love if you could articulate a little bit about how AVIM works. Sure. Maybe review some of the data that you've generated so far. And it's cool. For both our lead programs, we talk about being very much in the midst of a renaissance of foundational technologies in the two large cardiovascular markets, whether that's cardiac rhythm management or pacing, which is what our AVIM program leverages, or our Virtue program, which is leveraging balloon angioplasty. We're finding new ways to use established technology to have impact on more patients and indications. AVIM is a great example. So AVIM refers to atrioventricular interval modulation therapy. And really, it's a way of programming a well-established device, a dual-chamber pacemaker. We don't change the hardware, how it's implanted, where the leads are positioned. Actually, that's changing on its own. There's a big movement to what's called conduction system pacing. We just are running a different program that directly affects blood pressure and does so through a very potent and actually immediate mechanism. So the AV part, we reduce the timing of atrioventricular contraction. Therefore, you're reducing ventricular filling and affecting cardiac preload, which is a main driver of blood pressure. Less filling, less contraction. We really can actually, with this pacemaker, tune in, substantially lower blood pressure on the first beat, often double-digit millimeters of mercury reduction in systolic blood pressure. The key, though, is that interval modulation. So the body is always attuned to and watching changes in blood pressure. And our therapy is really based on taking the first mechanism and varying AV timing, and actually really varying blood pressure so that we prevent compensatory reaction of the autonomic nervous system, so really affecting sympathetic tone, and prevent a compensatory reaction of the blood vessels, so change in peripheral resistance. So it's a therapy that, just by pacing differently, lowers blood pressure, affects preload, afterload, and autonomic nervous function, which, by the way, are the three targets that we prescribe drugs for. So we understand the mechanism. It's complementary to medical therapy. Once again, because it's in a pacemaker, easy to see actualized. And the first patient population that we've partnered with Medtronic on is treating hypertension in the existing pacemaker population. So it's about 1.1 million pacemakers implanted worldwide. The U.S. is the largest market. Upwards of 70% of those patients have hypertension. It's the number one comorbidity. And it's an older comorbid, higher-risk patient population. So we see an opportunity to commercialize with Medtronic, commercialize this into their existing large dominant market footprint, help them grow that footprint, help them establish higher price points and higher profitability while actually significantly impacting this condition, which drives heart attack, stroke, progression to heart failure, progression to end-stage kidney disease, all the key things we worry about with older patients. So it's the first therapy we're running, our pivotal now. It's an interesting study, really double-blind randomized bioelectronic therapy study because all the patients are already getting the implant. We ran two prior studies using our own device, including a double-blind randomized study. Think of it as our phase II. The data has been outstanding. So the absolute effect on ambulatory systolic blood pressure from AVIM in the last study, the MODERATO II, was 11 millimeters of mercury. It was superior to control at six months of over eight millimeter difference, and these are changes in blood pressure, talking about ambulatory systolic blood pressure, that significantly 20%, 30% plus reductions in your cardiovascular risk, we think really can change the course of patients. That first market opportunity in treating the pacemaker population, we think it's as much as $2 billion of upside for Medtronic in terms of pursuing the opportunity, but there's significant opportunity to then be able to take the therapy, same device, but go after maybe a targeted small population, hundreds of thousands of patients that have very significant blood pressure disease with comorbidity and expand the market for devices, and we see that as a huge additional opportunity. Would require an additional deal with Medtronic, but we think that's a likely outcome as we progress. A couple of follow-up questions there. I guess first, maybe just cover for folks who might not know the way the economics work with Medtronic as you've constructed them. Is there any ability for you to get additional reimbursement based on the study outcome? Great. First off, we have a revenue share. There's a formula, but really we express it in dollars. So assume no change to reimbursement. Orchestra will make between $500 and $1,600 on every pacemaker, every AVIM-enabled device Medtronic sells. And keep in mind that could be a market of 750,000 patients every year worldwide that would have hypertension and need a pacemaker already. The 500 is the per-device minimum outside the U.S. It's a materially higher number in the U.S., Japan, China. Then there's a way we participate as a percentage of the overall ASP. That gets us to the 1,600. So I would expect that in markets like the U.S. and Japan, we're on the high end of the range. I'd say for a lot of Europe, we'll be on the lower end of that range. When we look at a royalty opportunity, if you take the midpoint, $1,000 would be the low midpoint. This is hundreds of millions of dollars of royalty potential. Obviously, we'll only win if Medtronic also wins significantly. Add on reimbursement. All of that assumes that we take advantage of established reimbursement structures where oftentimes the hospitals are beneficiary of bundling and contracting pacemakers because they are sort of a commodity-type important but commoditized device. We do think that there are clear pathways for AVIM to make those devices eligible, let's say in the U.S., for both transitional pass-through and new technology add-on payments. We could choose to take advantage of the breakthrough pathway to make that a little more straightforward. For renal denervation, obviously Medtronic's other hypertension therapy, which we think is a great thing to have in their portfolio alongside our technology, that pathway provided now nice reimbursement, should be about a $14,000 payment. So certainly something we at Medtronic are looking at that would enrich the opportunity and make sense given the clinical impact both for Medtronic and for Orchestra. We participate in additional upside that Medtronic can see through add-on reimbursement. So something we're looking at, but we'll see how that unfolds as we progress. There's a question I wanted to ask. I mean, Medtronic is kind of leading the way in hypertension now with renal denervation. With the partnership, how do you see those working together or complementing each other? Sure. And I think the best thing is to look at the clinical studies as to where the two therapies have been studied. And it really paints a picture of a continuum of care that I think Medtronic could build their 2030s decade around. Renal denervation has really been studied in younger hypertensive patients. When I say younger, patients generally in their 50s. And the label really is focused on patients either aren't benefiting from or can't tolerate or don't want to tolerate medication. Certainly, they did a great job with label. There's a big opportunity there. They've focused on treating patients with both systolic and diastolic disease and haven't really focused on older patients with isolated systolic hypertension. Meanwhile, AVIM, our patient population is very much a pacemaker population, at least what we've studied. That means patients that are in their 60s, 70s, even early 80s. Huge prevalence of isolated systolic hypertension in that population. That's really the hypertension we see in older patients. Higher risk, more comorbidity. So as Medtronic and ReCor, or Medtronic's really leading the way, are establishing that call point and referral pattern for hypertensive patients with renal denervation, we think there's a clear bridge or connection that can be made to their strong call point in active implantables and pacing. And that high-risk hypertensive population where we see patient flow in the future, you could have an already in patient that now needs an additional therapy a decade later, or an already in patient that isn't really eligible or isn't getting benefit, that still wants something that's always on, programmable, potent, and doesn't have the adherence compliance issues that we have with medication, or at least doesn't rely on the same patient compliance. So we like what Medtronic is really putting together in a portfolio. We want to see them win big. And we believe there's a huge opportunity for renal denervation, as obviously we believe in the AVIM opportunity. Maybe you give us an update on the pivotal study. Sure. It sounds like you're out there shaking the trees to enroll some people here. It's great. I mean, we've had phenomenal reaction from the clinical community. I mean, this is different, taking something they do every day and making it exciting. That said, it's new. We're asking EP Labs now to think about their patient population from a different way. It's not an implant study. We're actually downloading the therapy. I think we're pioneering the study. We're doing something that has strong conviction. Just learning from the early experience about how we make it easier to find patients, to engage those patients, and get them to qualify. We just announced one of the things we worked on this year is it's a download study that allows us to enroll patients that have received a pacemaker, Medtronic pacemaker, and then qualify. Initially, we only had a 90-day window after that new pacemaker implant. And what we worked on in the last number of months, but really only talked about to the public a couple of weeks ago, was that we've expanded that window out to a year. Actually, look backwards a year. We have a lot more flexibility to roll the patient in during that one-year follow-up. Blood pressure, we think, tends to be lower after a procedure and tends to normalize. And importantly, we can help the physicians engage their patient population. They now can consent a patient prior to implant. Previously, we weren't able to do that. So we're learning in real time, taking everything we're learning and seeing in the clinic and trying to make sure that we take those best practices in the U.S. and in Europe. And maybe we'll consider some additional countries as we move forward. It's a 500-patient study. So we have some work to do to enroll it. I think it's the hardest we'll ever have to work to find patients for this therapy. And there's strong conviction at Orchestra, at Medtronic, and we think amongst the physicians that are participating that we're going to see good data. So people are excited to do the work. Speaking of the data and the pivotal, you're still thinking the pivotal rolls by middle of 2025? We haven't updated our guidance, but one of the things we're looking at, and we said in our queue, is we're going to look at enrollment rates now that we've really started to benefit from these protocol changes, and when we update, when we do our next year-end update in March, we'll really either reaffirm or probably be more specific both about enrollment. What really people want to know is when we think we'll have the top-line data. The primary endpoints, which are between group difference and ambulatory systolic blood pressure, and then the safety endpoint is really looking at, we know after now almost 70 years of pacemakers, what are the expected or anticipated serious adverse events? We're looking at three months. Do we see anything that's unusual at unacceptable rates, so those are the primaries. We both measure at three months from enrollment. So enrollment really defines kind of a nice window for what's probably the most important data inflection point for Orchestra, our first big primary endpoint release, and so we hope by the end of March to be able to be clear about both timelines. Great. And I know you said in the beginning that you can often see a double-digit decrease in pressure with the first beat. Maybe talk a little bit about the data that you've produced so far in the Moderato series and how translatable that would be to the pivotal study? Yes. Once again, that was a good pilot, double-blind randomized study, same population, pacemaker patients. They got our device, actually. So we thank the patients for being part of that. But uncontrolled hypertension despite one, two, or three meds. Actually, we didn't cap it in that study. Actually, a little more medication has to be a maximum of three meds in the BACKBEAT study. So we think it's a really good indication of what we can see. Frankly, there's some things in the protocol in terms of how we're including and how we think the therapy might be working even better that give us hope that we'll see even better data. Doesn't really get much better than the Moderato II. So 11 millimeters reduction in ambulatory systolic, 11 versus a three-millimeter reduction in control group. So we were highly statistically significant, superior by over eight millimeters in terms of ambulatory. Safety, we looked at MACE events at six months. We had none in the treatment group, a 14% rate in the control group. We don't need to prove a safety advantage, but we are lowering the number one driver of events in terms of systolic blood pressure, so we're optimistic about the long-term safety profile, and so we would hope to replicate, if not improve on that data, but just I would note, five millimeters is viewed as clinically meaningful, and we've seen approvals for drugs and devices on lower differences. All the renal denervation devices really show between group differences of two to four millimeters, so the kind of data we're talking about is extraordinary, beyond what we need for approval, but we think representative of what this therapy can drive. The last couple of minutes, maybe we could talk about the SAB program, your second program. I'm going to talk really quick. So I guess to cover the most important points, maybe give us an update on where you are with renegotiating with Terumo, your partner. And then maybe talk about the early signs that you've seen for this market given Boston's launch of the AGENT device and how you may stack up to them. So TCT was a few weeks ago, which is the big interventional cardiology conference. And we've seen a trend in the last few years. This one was kind of the topper. The old boring stuff of treating coronary arteries is now all about drug-coated balloons. And here in Europe, it's been that way for a while. So we think Boston has a big release coming with Agent. They were bold enough to be the first to say, "Hey, we're going to get approval in the U.S. to do a randomized study with a paclitaxel-coated balloon." The data clearly showed they were better than a plain balloon, but still high target lesion failure rates at around 18%. What also got answered just after TCT, as you know, is how are they going to get paid? They're charging a lot of money for that balloon. They got their add-on reimbursement approved, at least for outpatient. We think the inpatient will come. They're charging upwards of $5,500. That was a looming question at TCT. We want to use this device. How do we afford it? That opens up a monopoly for Boston in a market that I think if you talk to interventional cardiologists, how would they be treating coronary artery disease in the future? Not just ISR, but at TCT, they're talking about large de novo vessels. We're going to try and use balloons and only stent when we need to. Huge sea change. The other thing that came out of TCT is a lack of differentiation between coated balloons. Virtue is really the only non-coated balloon in the market. And what we really sought to do is take a drug that has been on every stent, sirolimus, that we know has the best safety and efficacy profile, but see if we could replicate or even improve on the pharmacokinetics, the tissue delivery and tissue release profile that we know from a stent. And we did that. So we're able to deliver our Sirolimus EFR in larger doses and keep it in tissue the same way that a stent does. Drug-coated balloons with sirolimus have fallen way short of that, a fraction of the drug that's on a stent. So we think what that means is you can show better efficacy. We saw it in the clinic. Our target lesion failure with Virtue in our pilot study was 2.8%. In a comparable population, Boston's was 14%. So we think we have an improving drug in a system that's better when we eliminated the procedural challenges of a coating, loss of drug, particulate, needing to rush. So we think we have a product that will work better for physicians, have better outcomes for patients, taking things that are known and leveraging that. Your last question, I'll jump on Terumo, is we're actively engaged with Terumo. They've gone through significant leadership changes in the organization in the first parts of 2024. and I'm actually heading back to the U.S. to see some of their team members at VEITH Symposium this week. So we hope to be able to resolve that and most importantly, get the product clearly into a pivotal trial and a series of trials as we move forward. We think it's the best class in what will be the future of how we treat artery disease. Great. Well, I think we have to end.