Good afternoon, everyone. It is my pleasure to introduce today David Hochman, Chairman and CEO of Orchestra BioMed, a biomedical innovation company accelerating high-impact technologies to patients through risk/reward sharing partnerships with leading medical device companies. With that, David, I hand the stage over to you.
Appreciate it. I will go over here. It is great to be here and to have the opportunity to present at the Wells Fargo conference and close out the event. Orchestra BioMed is, as Brian said, a company that is advancing high-impact medical innovations through partnerships. Today I really want to talk about, assuming I can advance our slides. There we go. I want to really talk about three things. Our business model, which is partnership driven, which we think is novel and capital efficient in the medtech space. Our two pivotal stage programs that address high impact unmet needs in two of the largest, most established medical device markets. Significantly, the backing we have from strategic partners and strategic investors that has us in a great position as we look at major catalysts coming forward.
Near-term catalysts funded through 2027, really in a position to drive value. The business model, I just want to explain briefly. What we do at Orchestra is focus on being great at innovation in terms of IP and products and clinical execution, and then structuring win-win risk/reward partnerships with strategics that we think are in a much better position to commercialize those technologies into large global markets. We look to those strategics to participate through commercialization, through their outstanding global relationships, and then to leverage their significant established operations and their strong balance sheets. What we do is drive proof through data, and you will see the two trials we are running and the proof we can bring to enable regulatory approval, and secure value through royalty participation.
What our partners get are growth programs that are insulated from the P&L burden of R&D as well as the operational burden of R&D. We have some outstanding partners and two really exciting pivotal stage programs that have common themes that really reflect how we see the world and what our opportunity and model can drive. First and foremost, the two programs, AVIM therapy, which is a potent way of treating hypertension delivered through a pacemaker, and Virtue SAB, have three common themes.
One, they target unmet needs and opportunities in two of the largest established markets in cardiovascular medicine. On the AVIM side, we are layering on top of the $4 billion pacemaker market, but looking at the number one comorbidity and unmet need, which is treatment of hypertension. For Virtue, we are looking at bringing a better treatment for coronary artery disease to a $7.5 billion established market. In both cases, you will see that we are bringing powerful new capabilities, but building those on top of proven technologies.
In AVIM, it's a therapy entirely delivered by a pacemaker. Virtue takes a proven drug, sirolimus, and makes a much more powerful delivery through angioplasty. Our Medtronic partnership and our last component is that these lend themselves to our partnership model where there is shared upside and better collaborative execution through partnership. I will talk about our relationship with Medtronic, which opens up a huge opportunity. We think an over half a billion dollar annual royalty opportunity for us and very significant growth and profit potential for them. We have a relationship with Terumo, a little more traditional right of first refusal relationship for our lead application in coronary, which gives us optionality. We've seen a lot of capital into the company from those partners. Medtronic's invested or paid us more than $80 million.
We brought in a great strategic capital investor in Ligand last year that's contributed $40 million and also has a revenue interest in our royalties. Terumo's also invested or paid us $65 million. In total, 21% of the company is owned by strategics, and we have two great long-term fundamental healthcare shareholders in RTW and Perceptive. I am going to dive into the AVIM therapy program, which is importantly our most advanced program. We're going to wrap up enrollment of our pivotal trial before the end of this quarter and see data in the second quarter of next year. What is AVIM therapy? AVIM stands for Atrioventricular Interval Modulation therapy. It is a potent treatment for high blood pressure that works immediately. It has a substantial effect and a sustained effect through two well-understood and complementary mechanisms.
We lower blood pressure immediately by pacing the heart with a very short atrial and ventricular timing in terms of the contractions. This reduces the filling window of the ventricle and immediately reduces cardiac preload. Blood pressure drops. The body's going to react to that. Key to our IP and mechanism is a second part, which allows for a sustained effect where we're changing the AV interval or modulating it so that that reflex response doesn't happen. By that, we're also affecting cardiac afterload and sympathetic tone. Importantly, those three targets, preload, afterload, and sympathetic tone, are what we target with pharmaceuticals to treat hypertension. Patients receiving this don't need, at least in the first indication where we're treating hypertension in pacemaker patients, they don't need a new procedure. It's the same device.
The therapy can be programmed the same way those devices are programmed, and it's running in the background, really overcoming the biggest challenge we see with treatment of hypertension, which is compliance, and here it's patients don't need to do anything for AVIM therapy to benefit them. Hypertension is the number one modifiable risk factor for death and disease worldwide. It affects 1.4 billion patients, and I really want to highlight the fact that if you can bring systolic blood pressure down by 10 mm of mercury, that can have profound effects on relative risk of heart attack, stroke, progression to heart failure, progression of atherosclerotic coronary disease, and kidney disease. When we look at our launch population, which is the pacemaker population, this is a high-need population where over million patients every year are getting a pacemaker that also have hypertension. It's the number one comorbidity.
And let's keep in mind that pacemaker patients are older, between 65 and 85 generally. They have known comorbidities and are at higher risk. Given that as our launch population, it is really important, given the model, that Medtronic, who is the dominant global leader in cardiac pacing therapy, will be the commercial engine for this therapy under a partnership that we put in place in 2022. What we brought to the table was the technology and intellectual property. We have nearly 150 issued patents on AVIM therapy, including a large body, around 125, on hypertension and nearly 25 related to heart failure. We ran two prior studies. I'll summarize some of the key data from MODERATO II, which was our double-blind randomized pilot study, and we are the sponsor and are funding the pivotal trial, the BACKBEAT study, which I'll also describe.
We get uncapped significant royalties on future sales of AVIM-enabled devices. I'll walk through those economics. What we have in Medtronic is the global leader. Medtronic, in our estimation, controls half the global market, more than that in the U.S. They have exclusive rights to the launch market, which is a treatment of hypertension in the pacemaker population. They're incorporating our therapy as firmware in their next-generation transvenous pacemaker and in future generation dual-chamber leadless pacemakers. And they will be responsible for regulatory submissions, manufacturing, marketing, sales, and support. So our role really shifts significantly upon success of the trial. The market opportunity for this therapy in the launch market is quite significant. The pacemaker market is one of the most established markets there is in medical device. Been around for seven decades and was essentially the core business around which Medtronic was built.
That market has been commoditized, but it still is a $4 billion global market, seeing about 1.4 million implants every year. Upwards of million of those patients have hypertension. As I said, the number one comorbidity. We see opportunities to help Medtronic grow their top line, their bottom line, and their market share, one, by enabling differentiation and clinical impact that can lead to premium pricing that we think could grow the market by as much as $1 billion for Medtronic. And we see an enhanced reimbursement opportunity that we're really increasingly excited about. Importantly, we have two Breakthrough Device designations for AVIM therapy, and that could drive another $1 billion of growth. We get to participate meaningfully through our royalty interest. We think that annual royalty opportunity is $500 million or more for Orchestra.
And it's important to note our revenue share expressed in dollars starts at a minimum of $500 per device, and limited by the current payments and reimbursement can go up to $1,600. The minimum $500 million is for outside the U.S., excluding China and Japan. There's a higher, materially higher minimum for China and even higher for Japan and the U.S., but it is uncapped. So higher reimbursement could lead to even higher royalties than this range, and we're excited about that opportunity. So once again, very significant royalty, but with significant revenue and profitability implications for us and Medtronic. We entered in this partnership in 2022 after more than a decade of evidence development, both pre-clinical and then clinical of our therapy, and now are nearing the completion of the BACKBEAT pivotal study that we've run in collaboration with Medtronic.
Here is the key data from MODERATO II, which is the pilot study. What you are seeing here is, first off, consistently greater than 10 mm. Remember that 10 mm mark in terms of its material impact on risk. Greater than 10 mm consistent signal of efficacy. What is notable is first on the left before randomization, both in MODERATO II and in our BACKBEAT study, patients have AVIM therapy set up. As we see, an immediate blood pressure drop. To qualify for randomization, they need to see at least 5 mm of drop. 97% of our patients in this study that qualified for randomization saw that drop, and in fact, the average was 13.2 mm. We look at that through the lens of ambulatory systolic blood pressure. Patients are wearing a device that is measuring blood pressure 40 times for the full day.
We saw over 15 mm on day one, statistically significant versus control, and at six months, significant results over 11 mm. Long-term results consistent. Safety looked better, and medication burden actually trended down for our patients. We are looking at disease-modifying effects for blood pressure, but also when we think about an older comorbid population, significant challenges in adherence, compliance to drugs. This is an always-on therapy running in the background. It can target pulse pressure. A lot of these patients have isolated systolic hypertension, and they have significant heart failure risk. We have also seen improvement in cardiac function, both in terms of diastolic function and positive reverse remodeling of the ventricle.
So really a therapy that is looking like it not just treats blood pressure risk, but improves function and can be a potential treatment for heart failure. This is the design of the BACKBEAT global pivotal study that we have been running in collaboration with Medtronic that is looking at a very near-term milestone of completion and enrollment. In total, we are looking for 284 patients we think will ultimately over-enroll. Here we are using Medtronic's device platforms, their commercial premium platforms, and we have been screening patients, enrolling patients that previously were implanted, maybe very recently or up to five to six years ago, with one of those devices.
We screen them for inclusion/exclusion criteria, but mainly we are looking for uncontrolled hypertension despite being on one, two, or three classes of antihypertensive medications. The patients that qualify, once again, they get a download, in this case, of the therapy. They get set up with AVIM. They have to meet that same criteria of a least 5 mm response. We saw it was 97% with 13.2 mm in MODERATO II. Everyone that randomizes into the study has been a responder. We turn the device off, they randomize and blind it to the patient and blind it to the physician.
Essentially, the treatment patients get AVIM turned on. We follow the patients for three months for the primary data. We are looking to be superior in terms of the change in ambulatory systolic blood pressure to medication alone. We are pursuing that with a lot of confidence. On safety, we are looking at a single-sided comparison to the long history of anticipated serious adverse device events. We know what happens in these patients, and we are looking for is there a signal from AVIM of unanticipated events. Being deep into enrollment, we also are proceeding with confidence because we have not seen that. Finally, on secondary endpoints, we will blind through 12 months to get additional data on efficacy, safety, medication burden.
The trigger for regulatory submission is going to be the primary data, and we're really clear between us, Medtronic, and FDA on that pathway. This is what the pathway looks like. So near-term completion of enrollment, we're aiming for late-breaking data presentation in the second quarter of next year of the primary data. I believe we'll have multiple presentations and publications beyond that. As close to that data presentation, we're hoping to see Medtronic get their submission in, first and foremost to FDA, but subsequently to global regulatory bodies all over the world. We think commercialization can happen in the U.S. in the first half of 2028 and globally over the course of that year. So very significant opportunities ahead for us and Medtronic with this program.
Beyond the pacemaker population, there is a large opportunity now to bring a device therapy based entirely on AVIM, essentially it would be a pacemaker implant, to patients that can benefit from the blood pressure and cardiac function benefits. We have two Breakthrough Device designations, one covering that 300,000-patient opportunity on the left, which is the pacemaker population, but another covering what we see as up to 8 million prevalent patients, up to over 1 million a year in the U.S. that could benefit from this therapy. So a significant growth opportunity, which we see as a global $16 billion market opportunity. Medtronic does have a right of first negotiation but would need to negotiate with us to secure those rights, and we think that is also something that can happen in the near future. I want to shift gears to our Virtue SAB program quickly.
Virtue SAB, now we're talking about treatment of coronary artery disease, and that market is going through a paradigm shift that I'll describe. Virtue is a unique technology in terms of that paradigm shift built for leave-nothing-behind treatment of the coronaries, and it's built on two proven technologies that we have enabled and combined in a unique way. The first is a drug called sirolimus. We have our own proprietary formulation called SirolimusEFR, or extended focal release. This is a proven drug used for a wide array of indications but has been used for years in terms of preventing restenosis after treatment with a stent. We have formulated it to facilitate ideal uptake, distribution, and extended-release, and I'll show you that data. Then deliver it in a novel way, in a non-coated way through an AngioInfusion Balloon.
Essentially, we're delivering liquid drug through pores in the balloon. So we have none of the drawbacks that I'll talk about of all of our competitors that are drug-coated balloons. The market we're addressing is going through a paradigm shift. The $7.5 billion coronary intervention, or PCI market, is moving quickly towards leave-nothing-behind treatments driven by drug-eluting or drug-coated balloons. We think at least half that market's in play for that technology. In the U.S., there is one approved device. It's called the AGENT Paclitaxel-Coated Balloon from Boston Scientific, and that device is reimbursed and priced at north than $5,000 per balloon. Around the world, we're seeing 20%-25% of PCI and climbing shift to these technologies already. What is compelling about Virtue, and we'll really walk through this, are five things I'll explain very briefly.
One, in drug-eluting stents, the drug we're using, sirolimus, won hands down. It showed that it was more effective and safe than paclitaxel, and paclitaxel disappeared from stents almost 20 years ago. The issue, though, is that sirolimus has to be delivered the right way, and this data you're seeing here is from Medtronic's own experience with drug-eluting stents. They started with a fast-elution stent called Endeavor and ultimately had to replace it with a slower-elution stent called Resolute. If you don't get sirolimus the right way into the tissue, it doesn't work the way it should.
We shift now to the emergence of drug-coated balloons. Most of the drug-coated balloons, there's over 13 approved in Europe, deliver paclitaxel, including Boston Scientific's, which is on the market, and Medtronic's, which is not yet on the market. All of those drug-coated balloons have the same drawbacks. You can only coat so much drug in terms of the surface area. You lose most of the drug just transiting to the lesion, and you create particulates, which isn't great in terms of potential emboli risk.
When we look at sirolimus, though, the key and what's ultimately brought paclitaxel back is the difficulty of matching the elution kinetics from a balloon. We've been able to solve for that and in fact improve upon it. You see with Virtue, relative to the middle panel, which is XIENCE, the number one selling stent of all times. It's still on the market from Abbott. We actually deliver 10 times as much drug and keep a 10x higher dosing, this is porcine models, than what we've seen from published studies of XIENCE. If we look at sirolimus-coated balloons, and there's two that are undergoing IDE studies or nearing the market, we see significantly less drug at 28 days than what XIENCE or other drug-eluting stents deliver.
The clinical results for those sirolimus-coated balloons really follow the PK. They should be, because of the drug, better than paclitaxel. They're not. In fact, it looks like some of them are worse. So we see a great opportunity for Virtue and a clear data signal from our pilot study when we compare it to the Boston Scientific AGENT balloon. This is really looking at the single layer of stent cohort in the treatment of coronary in-stent restenosis. On the right, you're seeing the published three-year data comparing AGENT to plain balloon angioplasty. That was their comparator. On the left, you're seeing our pilot study data, and the endpoint is target lesion failure. You want a low result because you're looking at both adverse events and need to retreat. You can see in the first year, in the single layer restenosis, Virtue was 2.8% compared to AGENT's 13.5%.
Over three years, though, AGENT's numbers climb significantly, almost 100% over three years, whereas we see a flattening of that curve quite significantly. This data has us really excited, particularly in a study where we actually had angiographic follow-up, which actually drove some of those events. So we're now embarking on, started late last year, enrollment of a IDE pivotal study that is going to compare Virtue directly to Boston Scientific's AGENT. Success is based primarily on a non-inferiority endpoint, but we do believe that we can play towards our secondary test, which is superiority. We've built a product to differentiate from the field, and we think the AGENT balloon is a great target comparator because it is a good indication of all of, in our opinion, drug-coated balloon performance. This trial is in the earlier stages of ramp-up, but once again, this is an IDE pivotal.
Terumo has been at the table with us, has ultimately invested or paid $65 million. They have a right of first refusal for the coronary rights, but a response time that is about 30 days if there's a transaction we want to do. We have optionality and the ability to talk to a wide array of partners. We've identified up to 10 potential partners. Just noting that one of the products I talked about earlier was purchased in terms of upfronts and milestones for over billion dollars by Cordis a couple years ago. Precedent transaction at least gives a sense of potential value. We see both of these programs I talked about as platforms with pipeline expansion.
We see that opportunity I described in detail for treatment of hypertension in the pacemaker population, addressing an up to $6 billion TAM, but a $16 billion potential TAM for expanding into hypertensive heart disease. Same with coronary, multiple indications with the potential to expand to peripheral and beyond. We've got a great team. Really proud to lead a team that actually includes eight executives that have run as CEO, clinical stage development companies in med tech, a ton of experience at our senior leadership. Importantly, we don't need to be a big organization. We're reaching about 100 people. We think we don't need much more of that to do what we do best, which is drive this data generation. An outstanding experienced board with biotech and med tech experience.
In summary, we think Orchestra is a very compelling opportunity. We think we are right at the point of doing what we set out to do, which is deliver value for patients, for physicians, and for our partners, and for our shareholders, where we have a differentiated model. We have two programs that are addressing huge market opportunities with differentiated technology. A great partnership with Medtronic, optionality with Terumo at the table, and the capital we need to see us through these catalysts over the next six, 12, and 18 months. Happy to take any questions if we have time available, but thanks again for the opportunity to present. Thanks so much today. Take care.