Good morning, everyone. Welcome to the first-ever Heron Therapeutics Investor Day. I may be bouncing around here a little bit. I'm pretty excited to have everybody in the room and see a lot of friendly faces. So we really do appreciate you coming out today. Again, the purpose of today really is to try to give everyone a little more insight into what we're doing. I thought it would be a good opportunity for a lot of you to meet us face-to-face. I know we do a lot of things virtually now and so forth. So I think, you know, what you'll gather from today is you'll have a lot more insight into the business. We'll talk a lot more about the products, some of the things coming, but more importantly, get a chance to know each other and learn a lot more about Heron.
So before we get started really talking about, you know, the future of the company, I did wanna spend a moment and talk about sort of what's happened over the last 12 months and really how, you know, we sort of came to be in this company. So back in February of 2023, Velan Capital and Rubric got together and negotiated with a cooperation agreement with management. And that was really to facilitate change. I think what everyone saw in this business was an oncology franchise that was doing quite well. But, you know, clearly there were some headwinds that were faced with ZYNRELEF . And, you know, now that I've had a chance to be here a while, I would say that, you know, where the company, I think stumbled a bit was pivoting. When we didn't get the label that we had anticipated, COVID hit.
You know, there was a number of factors that happened all at one time. And the company really had not gotten to the point from a financially being managed standpoint where I think we were able to pivot to really be in a commercial organization. Shortly after, I joined the board in February with, with Adam and Velan, it was decided to make some changes at the management level. So that's when I came into play. I joined the company in April and then really began to sort through the business. And the one thing that I, I do wanna mention here that I want you guys to take, when you leave this room is that, you know, we have gotten things under wraps financially and got our hands around this, as we like to say.
But the main thing that I think the company lacked that we have brought is really accountability. And accountability to the financials, accountability to each other, and, and really managing this business. And I think you'll see that as we go forward. But the one thing that I, I wanna try to relay as we go through the day and we'll talk about the clinical, value of the products and so forth. But when I first was exposed to Heron, it was at a national sales meeting, when we were launching APONVIE. And I'm, I'm two weeks into this as a board member. And I was really amazed as I talked to the salespeople, you know, again, the company's I don't wanna say in disarray, but there's a lot of things going on change-wise.
And yet, you know, I've got Reps coming up to me telling me exactly how great these products are and what they do for patients. And, you know, I was expecting something different, I guess. And so I'm hoping as you leave today, you get that little bit of sort of special sauce that we see on a daily basis that, again, we're trying to communicate and we're seeing happen internally. But, I'm hoping that today you leave with that as well and you kinda understand a little bit more about sort of the passion and the people here, and, which is really what drew me to this initially, so.
So again, just looking at some of the events that happened last year, again, when I joined, it was pretty clear that we needed to do some things, from a management team level, just changing the culture, changing the way we did things. But the two biggest, I think events that, that I walked into and tried to really change were, as we looked at commercializing products, you know, the manufacturing agreements we had in place were just not. I, I couldn't go back and rip up every contract, but we're able to renegotiate some things with Patheon. Adam and I made a trip over to Austria. We visited every manufacturing plant we had, and we're able to really change some things there. And I think you guys have now seen that that's, that's being reflected in COGS and, and better gross margins and so forth.
The other thing was that, again, we really didn't have a forecast in place, nor did we have any pathway to profitability. And so the spends seemed to be endless. And, so we were able to put together a forecast, find a path to profitability, and then determine how much money we would need, you know, to get there. And so we did a $30 million equity financing, followed up by debt financing of $50 million, and we brought $25 million of that down. The takeaway from all of that is that we have enough cash now to get to profitability and beyond outside of any, you know, type of M&A or, or something like that. So again, the company's really well-positioned financially.
The really other two big events that, again, we're gonna dive into a lot today is, one, the expanded label, which we finally got, and, and having a label now that certainly competes in the market. And then really the big deal is with CrossLink. And, I'm gonna go into this more as we go through the presentation, but needless to say, we are more than pleased, with that, agreement and, really think it's gonna be a, a huge change for the company as we move forward. I wanna spend a moment and talk about our management team. Again, I know a lot of companies put slides like this up. I wanna point out a couple of things that I do think are unique. If you look at, the first two, Ira and I, so we've worked together now for 15 years in sort of this CEO/CFO role.
And we've had two successful exits at two companies, and this is our third together over that timeframe. So the point of this is it's a lot easier to come into a situation like this, make change, you know, exactly there's kind of a yin and yang effect, you know, to that. I'm not sure if Ira would call herself yang or yin, but anyway, so we hit the ground running and worked, you know, quite well together. The other two people I wanna mention here is Ryan Craig and Melissa Jarel. Both of those guys worked with us at Veloxis, again, kinda putting the band back together type of thing. So again, very easy to communicate. They know what to do. When we talk about budgeting processes and that type of thing, they know how we function, so it's made it extremely easy.
One thing that we didn't have that we were able to add, and I wanna talk a little bit about this person's background, is Bill Forbes. So Bill heads up all of our development here at Heron. And he'll laugh about this, but locally in our area, Bill was really what I think a lot of people would say were the brains behind Salix Pharmaceuticals. And he was responsible for 14 approvals there. The reason I bring this up is that we're gonna talk a lot about what we're doing commercially and how we're gonna move forward, but this company has the capabilities to do a lot more than that.
And again, as we, you know, look down the road and think about acquisitions and doing things that will allow us to stay profitable, we also will, you know, move into development and look at things that, you know, we can add to the pipeline and certainly have those capabilities. So again, we feel like we have. I know we don't like to use the term rock star anymore, but I think we do really have a rock star when it comes to development. Outside of that, Rob Solomon and David Barozzino kind of are the, if you will, the legacy employees that we brought in. I think the success that we have on the oncology side speaks for itself. Rob's team consists of a few folks that have, you know, 30 years of experience in this on this side of the business.
His group really has a lot of capacity to do other things. Again, as we look at M&A and things like that, or certainly things we could do product-wise on that side. And Rob is, you know, just doing a phenomenal job of leading that team. David Barozzino. We were laughing at these slides. He's the only one not smiling. And I think, hopefully when we have this next year, the products have taken off and he has a big smile on his face. So now, but in truth, when we promoted David in October, it really changed the face of the company from the standpoint of linking that sales force to the new management team. And we were having a tough time with that. You know, imagine we're coming in, we're making all these changes, people are leaving and so forth.
David was really key in that. If you look at kind of the product growth since then in all of our products, things are really beginning to change. Again, we're gonna talk more about that, but I think David has really been a key in that. So the last and certainly not least is Kevin Werner. Kevin comes from the clinical side. He was a KOL for us, has done a lot of speaking. He probably has more experience with these products than any of us, and he was really the missing piece to our team. I think you guys are gonna hear Kevin speak here shortly, and I think it'll speak for itself when you hear him talk about the products and his knowledge and so forth.
So the point of all this is we have a team I think that works very well together that has worked well in the in the past, and we've put the missing pieces to this team to really position the business to move forward. Excuse me. Okay. I showed this slide on our last earnings call, but I wanted to bring it up again just to really show the impact and again talk about sort of where we were and where we are now. When I joined Heron, I think we were in the 220-employee range. And now we'd like to settle in at kinda 140 range. I think we're now at like 125, 126. But, you know, with that, we were able to increase revenues year-over-year, if you will, from $29.6 million to $34.6 million, as you can see on this slide.
I talked initially about when I joined the company was getting inventory management in place and really improving our COGS by negotiating with our manufacturers. I think the numbers speak for themselves. We've gone from a 43% gross margin to this past quarter was 76%. So it's really changed the face of the business and allowed us to, you know, certainly create that pathway to profitability. If you look at the expense management, again, you know, we've had a $28.2 million turnaround in 12 months. So, what I would tell all of you who are investors in this, we're doing the right things. We're gonna continue to do the right things as far as managing the financials, financials. And again, if you look at the cash position, we're in a pretty good position there in order to have enough cash to get to profitability and beyond.
Now, although a lot of you may have been hoping today that we were going to change our guidance, I just wanted to really reiterate this and really talk about it a little bit. We put this out in, I think, Q3 of last year for 2024. And again, we gave a pretty wide range on revenue, reason being, you know, at that time, we knew we had a pretty consistent business on the oncology side. But if you think about ZYNRELEF and APONVIE, and as you see as we go through this, you understand sort of how these things could range a bit. I mean, at that time, we weren't sure about CrossLink. We were in negotiations, but, you know, we didn't know if we would have get that deal done, which we again, we know we'll have a huge impact. The VAN, we're still moving along.
And again, at this point, we have some surety around that, which we'll talk later. But and then the, the label. None of that had happened yet. And so for us to give that sort of range was really based on ZYNRELEF and APONVIE. So again, we're hoping as we go through the year, we'll be able to update this and, and hopefully improve upon that a bit. Again, just mentioning gross margins, we, we were at 76% last quarter. I think ultimately we're gonna sort of narrow in around the kinda lower 70% range. And, we'll improve upon that a little bit as we go, you know, beyond that. OpEx, we gave a range of $108 million-$116 million.
Again, I think everybody's done the simple math of multiplying by four from this last quarter, which would take you to the low end of this. We have not changed that yet, but again, we're hoping to, you know, certainly stay to the lower end of that, which will allow us to get to profitability even quicker. And from an EBITDA standpoint, again, we gave a range of -$22 million-$3 million. And again, I'll restate this again. We do plan to be profitable by Q4 of this year. Okay. Before I jump off here again, I, I just wanna talk a little bit about what we wanna accomplish today. We think we have something very special with these products, and they really are different clinically. And very soon now, you're gonna hear our speakers talk about this. And I think, again, I want you guys to take really look at these products in this market.
And we're hoping to not only show, you know, the differentiation, if you will, with these products, but to really give you a line of sight to what does this market look like? I mean, you know, you can talk about things like, "Oh, there's 60 million procedures, and we're gonna get a piece of that." But we wanna really try to give you a little more detail on how we're gonna get there and what that looks like and the timing and so forth. And so, again, I think you'll leave here with a clear line of sight into really what the potential is for some of these products. Again, CrossLink, I get a lot of questions about this. We have the guru in the room today, with Mr. Thomas Fleetwood.
He's the CEO at CrossLink, and I think he can give his perspective on, you know, what this has looked like so far and just really his experience in the market is, as good as anybody, if not better. And so, I think we'll give you a lot of insight into CrossLink and how that's going. We're also gonna update you on the VAN and the prefilled syringe. Again, we got a lot of good news there, and things are moving along. We'll also spend a little bit of time on the oncology franchise. I know there's some questions about the ANDA. And, we really want to put, you know, sort of so you can see really visibly the consistency of where we think this is gonna head for the future. And, hopefully we can clear up any questions, on that.
And then really last, again, I mentioned the management team before, but the one thing that I want you guys to see up here as people speak and you and you see this is that we really do have a special team together that truly does function as one to hopefully deliver shareholder value to all of you, which is hopefully why we're here today. So with that said, I thank you for your time, and I'm now gonna turn things over to Ryan.
Thanks, Craig. I appreciate that. So I just wanted to take a quick second and, and characterize the rest of the day. As Craig mentioned, you're gonna get a good, in-depth view of our clinical differentiation of our portfolio. But I also wanna talk a little bit more about the team that we have in place.
You know, as Craig mentioned, my experience, I spent 15 years at Salix Pharmaceuticals, and that was really my first entry into pharmaceuticals. I was an inside sales representative, transitioned into marketing operations and then inline brand marketing. Throughout those 15 years, I, I sort of call it like the juice. You're building something special. And I felt like every 12-16 months, we either had a new indication, new label, new acquisition, again, led by Bill Forbes and his effort. At Veloxis, we got the same experience, right? I spent 5 years with this team, with Craig and Ira and Melissa, Ingrid, etc., building something from the ground up. And that's the team that you have in place here, is those people that are looking for those opportunities.
So as soon as I found out that Craig landed at Heron and started to pay a little bit closer attention to the team that he was putting in place, I'm the one that reached out to Craig immediately and said, "I really wanna be a part of that." There was a couple reasons why. It was about the people that he was pulling together. At that point, he had already pulled over Ira. He had pulled over Bill Forbes. I said, "Oh, man, this is these are leaders that I wanna be a part of and I wanna follow." Then you look in-depth at our clinical portfolio and you realize we have a really good asset that in our portfolio that is gonna help a lot of different people. Commercializing these products is a fun ride for us.
You know, I think as you look throughout the day, you're gonna find that the past 6-9 months as this new team has been in place, it's really foundation building for what we're gonna deliver, in terms of revenue. Our portfolio makes a lot of sense in a lot of different areas. So as you know, we're sort of split in two different areas, oncology care and acute care. But what we really do is contribute to patient outcomes following these really important procedures or circumstances that they're in, right? Whether it's chemotherapy-induced nausea and vomiting on the oncology side or post-op nausea and vomiting on the acute care side or post-op pain, right? So we're trying to make these sort of severe, complicated issues a little bit easier on patients and a little bit better on patient outcomes.
If you look at our overall revenue contribution over time, despite all the changes that we've had over the past year as an organization, you can see we still maintain consistent growth. The oncology-based business is strong. You see that growing year-over-year. Quarter-over-quarter, Q1 2023 to Q1 2024, we had over 17% growth as an organization. So over time and as we continue to leverage APONVIE and ZYNRELEF and grow those businesses, you're gonna see this continue to stack onto a, an already strong base of business in the oncology franchise. So with that, I'd like you to hear a little bit more about our clinical story, from Kevin Werner, Randy Robbins, and Alan Rechter. Come on up.
All right. Thanks, Ryan. Thanks, everybody, for being here today. It's my, my pleasure to be standing in front of you as part of Team Heron.
I made the jump, three months ago to come be part of Heron, be part of something bigger, clinical pharmacist by trade. I had the pleasure of launching ZYNRELEF at my institution, had two and a half years of experience with it, and that's why I'm here today. We also launched APONVIE, which was another key cog in our wheel as far as what our facility's doing, enhanced recovery for our patients. Today, you're gonna get to hear from two experts. Besides myself, you're gonna get an entire healthcare envelope, if you will, from a facility basis. You're gonna get the pharmacy, anaesthesiologist, and the surgeon.
So it's gonna be a great picture for you guys to peer into why we believe the commercialization of these products is gonna happen, but more importantly, how we see it as the foundation, the foundation of healthcare, and how our systems are kinda transferring. So we're in the space right now where everything's about same-day discharge and throughput for our facilities, right? But we have to do the right thing for our patient. We have to provide the appropriate analgesia. We have to provide the appropriate post-op care and rehab and support for these patients to get them out of our facilities, through the facility, home safely with a good recovery, right? And so Heron Therapeutics, as we talk today, is gonna be this focus on these two acute products right now. But they are the foundation of that recovery.
So when we look at our products, our patients come to us, and their two primary concerns when they walk through the door, they wanna know, "Is it gonna hurt?" and, "I don't wanna vomit after surgery," right? So when you rank these things on a list, that's what patients tell you. They don't want nausea and vomiting, and they don't want pain, right? And Heron Therapeutics has the two best-in-class products. That's a strong statement, but we have the literature to back that up. Two best-in-class products for post-op pain, and for post-op nausea and vomiting, our patients' two primary concerns. And we talk about that throughput for the institution. Those are also the two most common things that keep our patients in the hospital. And they kinda go hand in hand. Once our patient starts having pain, guess what they reach out for? The opioids. What opioids cause?
Nausea and vomiting, urinary retention, things like that, so on and so forth, where we can't get the patient out of the hospital. So we need to stop or prevent those things from occurring to maintain the financial viability of our institutions. Both these products also commend themselves to the institution as far as ease of access and use. They're both ready-to-use products, essentially. So as far as pharmacy throughput, being there in the Omnicell, being able to go into an ASC, an ambulatory surgical center, doesn't require compounding or excess staff to provide these products to the patients. And they're also long-acting. So this is another differentiator. A lot of times, we start to think acute care, acute phase, control their pain. But when these patients are out of sight, they shouldn't be out of mind.
So we're moving these patients faster through our facilities now, through these same-day discharge models. But just because they go home, they shouldn't be out of our mind as far as, "Are we controlling that pain? Are we controlling that post-op nausea and vomiting?" So importantly about these products, for ZYNRELEF, we have 72 hours of postoperative pain management. For APONVIE, 48 hours of PONV prophylaxis. So these patients are out of our facility, but they're not out of our minds, and we're still providing that recovery for the patients. So now, we're gonna go into ZYNRELEF first and get the pleasure to introduce Dr. Alan Rechter, Orthopaedic Surgeon. He's gonna speak to his experience and the impact it's having for his patients.
Well, thanks for having me. I was involved actually in the clinical trials. So before this was a ZYNRELEF, it was an HTX-011. I h ave a high-volume ortho practice. And we do essentially this is kinda the trend. Everything has gone outpatient, so it's amazing. And since 20 years ago, in my training, you used to stay in the hospital 5 days when you had a joint replacement. Now you come in, you get it home, and you go, you know, same day, you're in your bed that night for good reason.
You know, they kinda figured out that the patients in the hospital are the sick ones, so the infection rates were higher and whatnot. So things that really kinda migrated in that trend. And then with clearly with, you know, the issues that they've had with inpatients, when they had the coronavirus, that was pushing people towards getting out of the hospital as well. So we saw a lot more people doing outpatient surgery.
So then he said, "We gotta be able to control their pain." So the problem was that they had this gap. They called it an efficacy gap. But what that meant was we had good local anesthetics. We've always had them. They were good for short, you know, six hours, eight hours. But we really needed something to go longer. And the problem is, if you think about this in terms and I describe it as such, if you went to the dentist and had your tooth pulled, you know you're gonna look like a chipmunk for three days. That's the inflammatory thing that everyone expects to see, but that happens everywhere. So the problem is you've got three days to try to cover, and you got these 12-hour products, and then you have this gap.
So the gap was solved with ZYNRELEF 'cause finally now we had a product that's gonna go for three days. We can get people we can get people through that three days. And when they said, "Why is it three days anyway?" I mean, Heron said, "We could have made this thing go for 30 days." And but they had talked to a lot of the surgeons, and they talked about that three-day inflammatory window, which is the critical period to get people covered. And if you can just put them on the backside of that, they just do so much better. So this really solved the problem that they had. So if you haven't seen it, this is ZYNRELEF. It is the first and the only extended-release dual-acting local anesthetic. It really comes in a box, which you can see out there, and open it up. Very stable.
It can stay basically in the box for two years, but it's designed to fit into some of the delivery machines. It's got a novel synergistic combination. So when people say, "What is it?" It's things that have been out for a long time. So when we're discussing with doctors, when you bring them that's something completely new, everyone's always skeptical about it. But, you know, bupivacaine's been around 20 years. Meloxicam's probably the number one go-to written anti-inflammatory that we have anyway. So people know both of these very, very well. So you go, "Well, what makes it special?" It was Heron's polymer. It was that Biochronomer polymer that they developed that will then break down and deliver that product over a three-day period. And by the use of it, it has found to reduce or eliminate the use of the narcotics.
And interestingly, when we were doing the trial, we had patients that had gone through a knee replacement. We'd see them in the office, and the guy said, "I didn't take any pain pills." I said, "No way. You never saw that before." There was never a patient, I will tell you, in 25 years in practice that had gone through a knee replacement that didn't take one pain pill. No, never saw it before. So we knew in the trial, this stuff works. And we could tell it worked based on that. So we said, "This stuff really does its job." So again, the timing was good and bad. Obviously, the coronavirus came right at the beginning of it, but really, it was during the opioid crisis. So before corona was in the news every single day, it was the opioid crisis, opioid crisis.
This was actually there, and it was solving that big problem. From an administrative standpoint, it's easy to apply. It comes in a single dose. It's a needle-free application. It's just spread into the tissues. It doesn't require any fancy mixing. Some of these other products, you have to mix them. It takes a lot of time to do it. And from a pricing and distribution, all this for a brand new product, it's really competitively priced. So if you, again, haven't seen it, it's there on the end of the slide there. It really looks like a honey-based consistency. We compare it to the gold standard, which is bupivacaine, or if you look at the liposomal. So some of the things with those, bupivacaine was fine, but again, it worked well. It just didn't last long enough. That was kinda the problem with it. Liposomal, it was better.
That was something that would go for 24 hours, maybe 36 hours. But those were really in the blocks. What they were kinda finding is in the surgical sites, they would last about 24 hours. So again, you weren't getting through that 72-hour period that we were needing to cover, but the ZYNRELEF did. And interestingly, the reason why it works so well, if anybody's ever had an abscess or seen somebody with an abscess, they're kinda these big, hot boils, painful. You go to the doctor, and you're like, "Doc, you gotta numb this thing up." And the doc will say, "I will. I'm happy to do it. But unfortunately, the local anesthetics don't work when they're very acidic like that. That's an acidic environment. That's what happens." So what they figured out was when you do surgery, you're creating a bit of an acidic environment.
The problem is, in every single patient that's having surgery, they have this little bit of an acidosis at the surgical site. Well, guess what? The local anesthetic, we already learned, they don't work very well there. But the meloxicam that's in the ZYNRELEF will normalize the pH. When you get the pH to be normal, then all of a sudden, the ZYNRELEF works. In fact, if you look at some of the slides that the company has, they would show they took the Biochronomer polymer first, and they loaded it just with meloxicam by itself. It was definitely better than the placebo. Then they did the Biochronomer polymer just with the bupivacaine, and it was better than that. But when you put them together, there was a synergistic effect. Why?
Because you finally got the acidosis under control, and now you got a product that can go for so long. So even with liposomal bupivacaine, as they're getting more acidotic 'cause you're not controlling it, there's no meloxicam in there, you see that there's a limited effectiveness of that product. So this is actually a video that we shot. I'll show it to you, and then I'll just talk a little bit about the evolution, on the application of it.
Hi. I'm Dr. Alan Rechter from Houston, Texas.
And I'm Marlene Shook, Physicia n Assistant.
We're gonna take you through the use of Heron's ZYNRELEF product in total knee arthroplasty surgery. Whatever technique that you like to use in knee replacement surgery doesn't change. Whatever implants you like to use, they're still the same. So you do your normal techniques. That doesn't change. Then when we get to the end of our surgeries, we all like to lavage. So here you see we've done the lavage.
We're now starting to dry the joint. I like to bend the knee up 'cause there tends to always be fluid around the post, and we dry it further. Once that is done, we begin our closure. We've gone to a running STRATAFIX-type suture, those running barbs. And what we do is we start from the inferior aspect and work our way to the top. But then we leave a little window about one inch above the patella there where you see we start to apply the product. And usually at this point, Marlene takes over, so I'll let her take over from here.
As you can see here, I'm placing the applicator tip in the knee, and I place it inside the suture line. You can see it on the medial gutter, midline. Here's the second syringe. Again, the medial gutter, the midline. Here's the lateral gutter. We just make sure it's spread evenly and everywhere. I close that gap with a 2-0 Vicryl. Then I use a STRATAFIX from superior to inferior to make sure it is sealed tight. I put the knee in range of motion, check the tracking. Then I do my normal stent closure with a 3-0 STRATAFIX, staples, and then soft tissue dressing.
At this point, the product's been applied into the joint. It's doing its thing. It moves around quite well, and it gives them excellent postoperative pain relief after joint replacement surgery with this technique. Thank you for watching our video. If you have any questions, consult your Heron representative.
So that actually was a little bit of an evolution in the application. So during the trial, the protocol was to make sure you put it everywhere. So we had the joint wide open, and you would squirt it deep in the tissues. And it was important to get it in the very back of the knee. In fact, for knee replacement and, in the portfolio, when they added the knee replacement to it, they actually had a whole separate arm that was different 'cause they a lot of the orthopedic surgeons said, "I think a lot of this pain that people are getting is coming from the posterior capsule of the knee. So it's critical. Let's make sure we get this in the posterior capsule." So we spent all this time getting it around the joint and posterior capsule, this, that, and the other.
We didn't need to do that. So what we learned, which we showed in the video here, is the product will self-spread. And once it gets into there and it gets to body temperature, it starts moving around the joint like crazy. In fact, the first few times I tried it, I put it in, then I reopened up the suture line to the dismay of my PA to do it. But I wanted to see what it does. And you take it through ranges of motion, and it goes everywhere. So the posterior capsule, we were spending time making sure it got in the posterior capsule. I always say it's like, you know, the oil in the pan of the car. It's gonna end up in the posterior capsule. Every patient's coming out of the operating room supine, so everything is draining into that posterior capsule area anyway.
We're getting terrific coverage. So really, the new application techniques, they're so nice because you're really just closing just like normal. You have a little bit of a window in there, and everything's going through small little windows. And it just self-spreads itself, and it does terrific. So it's way the, as far as the development phase, it started out with the phase II. And really, those were really more bunion trials and the open herniorrhaphy trials. When they went to the phase III, they kinda added the total knees. Those were the epic trials that you saw there. Around that time, they were just coming out with what they called the non-opioid MMAs.
So interestingly enough, if you just add, it was acetaminophen, so a Tylenol-type product and a celecoxib or a, you know, an ibuprofen type of a product there and just alternated them, those were the non-opioid MMAs. The pain relief was incredible. It really just augmented the effectiveness of any type of a medication. So you were seeing people that were taking a lot of pain medicines coming down. But if now you had a Heron product in there with a ZYNRELEF , like I said, that's when you were starting to see some of these patients saying, "Nah, I never took any." And again, we had never seen that before. And then it ended with the HOPE trial, which was a hernia trial.
The goal in that trial was just to see if they can send patients home with no narcotic pain medications, and in greater than 90%, they were able to do that. So to sum it up for my part here, we do believe that ZYNRELEF will likely form the foundation of postoperative pain management. Again, it is the first and the only extended-release dual-acting local anesthetic. And we talked about really, in essence, how it works so well. It just it's designed to really work on the inflammation at the surgical site with the meloxicam that's based in the product. And then that allows the bupivacaine to do its thing. And the special part of that, again, is the Biochronomer polymer that Heron developed. As far as from a pain-relieving standpoint, it is something that we have shown that it'll go for three days.
It's a 72-hour product. It truly is. In fact, we had heard about some of these other things that would go that long. They just never really did. And again, when we had nothing else, a day, day and a half is much better than what we had. But we now have something that actually really will go for 72 hours. As far as obviously the opioids and the issues that go with it, as Dr. Werner mentioned, when people are taking pain pills, you have constipation, nausea, vomiting, things like that. So as we can get those numbers to come down, then the patients are doing better. And all the hospitals are trying to get satisfaction scores. So it's big for them to make sure that their patients are getting out of there and having a good experience.
This has been able to really help with that. As far as the application, again, this comes really it's in a vial that needs to be drawn up. They're starting to move towards a prefilled syringe which will make things a whole lot nicer. But it's really not that hard to do it now anyway. There's so much happening in the OR, you know, for the scrub tech to draw that up. That's easy. Application's super simple to put in. And again, with the new technique that we found out, just get it in there. It'll spread itself around, and it does such a great job that it really doesn't change, and it doesn't add more time to surgery.
And then again, from a value standpoint, and I guess they can talk about that a little bit more, for a product that came out that's brand new, when I started talking to docs about it, number one, it's not very expensive. Two, because the federal government was trying to incentivize companies to get away from opioids, they have a pass-through status where there's some reimbursement for these. So a lot of these hospitals that are actually using the product can file and actually get reimbursed on these. So for a lot of them, they can actually trial it for nothing. All right. I'm gonna turn it back over to Dr. Warner.
Thank you, Dr. Rechter. It's amazing stuff. Just as we've seen in our institution, I'm just gonna take you guys through a couple real-world trials here 'cause as healthcare providers, as scientists, we remain skeptics. Sure, Heron goes through the process with the FDA, proves it once, proves it twice, proves it three times. The literature comes out. But then the hospitals, the institutions, the providers, they say, "Well, show me against this," or, "Show me a comparator," or, "What's, what's it like in the real world? Can I replicate that?" Right? So it's important always to look at the evidence and reveal the evidence to see where it stacks up in clinical practice. So the first poster presentation you see there is by Dr. Sah. And the comparator in that group is liposomal bupivacaine, brand name for that is, is Exparel.
So Exparel came to market back in 2012, and it touted the extended-release profile that had that goal. Did not receive that label from the FDA, though. A lot of people still implement it hoping for that extended analgesia. So ZYNRELEF, the first product with the extended-release label per the FDA, came to the market. And so many people wanted to compare it. How would it change practice? And in his results, he's seen quicker transfer to the PACU, farther ambulation, higher same-day discharge, less pain at discharge, less opioids used, and less severe pain. And to me, severe pain is one of the strongest metrics that we look at for our patients and most impactful. And why is that? 'Cause severe pain is when they reach for that opioid. Now, when they start taking that opioid, now they have the opioid-related adverse events.
Severe pain is when they won't get up and get out of bed and do that physical therapy. So severe pain really starts that snowball that impacts that patient's length of stay acutely but also changes the future perception of pain for that patient throughout the rest of their life. So the amount of pain you experience during the perioperative phase from the extent and duration of it changes how much pain you experience forever. Your body remodels those pain receptors as soon as that insult starts. So controlling that pain, moderating the pain, it's never gonna be zero, especially in total knee trials, but getting a baseline that's stable, that you don't have to use the crutch of the opioids, that changes that quality of life for that patient ever ongoing. The next poster you see there is against what I consider the standard of care.
The standard of care historically is the generic joint cocktail we would use in the TKA. So it's a combination of anesthetics, NSAIDs, some epinephrine. It works really well. It works really well for 12-18 hours. So when we've seen ZYNRELEF come through the clinical trials and beat bupivacaine for opioid reduction and pain reduction, we said, "Well, we gotta give this a try. We gotta give our patients this opportunity to have 72 hours of analgesia versus the 12-18 our cocktail would provide." We were really interested, though, how are they gonna impact the patients, or what was it gonna look like at hour 8, 12, 24 for those patients when it was stacking up against our cocktail and the efficacy of the cocktail.
We were very happy to see in our results, we saw a 50% reduction in their opioid use and about a 1.5-point difference in their pain scores. That's statistically significant but also clinically significant for our patients. They're using less opioids and having less lower pain scores. A lot of that was in the acute phase, that first day for those patients. We're seeing a lot of impact early on knowing that we could rely on this and send those patients home, discharge them in that stable condition. Beyond the clinical impacts here, you see a nice list there to a comparator. I know analysts love comparators and setting benchmarks and looking at things. The only other option in the market right now that's touted as long-acting is Exparel, liposomal bupivacaine. But you can see the clinical differences there.
From the clinical trials, the major pivotal phase III and II-B clinical trials, ZYNRELEF, greater pain reduction through 72 hours versus bupivacaine, lower opioid consumption, less severe pain. So all those checkboxes are for ZYNRELEF. Then you look at the economics 'cause finally, from a holistic perspective, economics matter in our health system. So we look at safety. We look at efficacy. We've documented all that. But how does the pull-through look? What do the economics look like surrounding a product like this? Obviously, there's the soft costs with length of stay and throughput for our hospitals. But just on a hard-cost perspective, you have lower acquisition costs. And you also have the favorable reimbursement pieces. As Dr. Rechter mentioned, we have pass-through status. So it means it's paid for outside of our bundled DRG payments that we typically rely on in the institution.
So that's a separately billable item for our HOPD patients and for our ASC patients. So ZYNRELEF is the standard of care now at many institutions and hopefully becomes the standard of care as we develop more evidence and get information out there. So that's our new foundation for multimodal pain management. But there's two arms to ERAS that I really look at and the two things that keep patients in the hospital besides postop pain. It's postop nausea and vomiting. So highly undesirable but also an underrecognized problem. When we looked at PONV in our institution, it was almost 30% was our PONV rate. Pretty shocking to realize. And it's likely because we have segregated providers, and not everybody's seeing that patient or following that patient all the way through their experience. You have some pre-op providers, and you have intraop the Surgeon.
It's really the PACU nurses feeling and seeing that PONV or your nurses on the floor. Maybe the surgeon doesn't witness it. But anaesthesia, they're the ones that's often termed responsible for the PONV patient. So I'm gonna introduce Dr. Randy Robbins, Anaesthesiologist, and he's gonna take you guys through APONVIE .
Thanks, Kevin. Yeah, I'm an Anaesthesiologist, and we take a lot of blame. I think the surgeons blame everything on us once they leave the OR 'cause we don't ever see them again. But I will say, I stand here today as a Physician that practices. We have a group of about 40 providers, and we do almost 40,000 cases a year. So we do mostly outpatient stuff. But I'm also a postop nausea patient. So I get horribly ill when I have general anesthetic. I puke from my toes every time. So this is very near and dear to me. And they talked about this. Pain and nausea are the two biggest things that patients are concerned about. Nausea is always their number one concern. Nausea and vomiting.
If you ask a patient, you give them $100 and say, "Hey, what do you wanna spend your money on to not have in the perioperative period?" They'll spend over $30 on postop nausea and vomiting alone because there's nothing that, that's more miserable than having a knee replacement or having jaw surgery or having your tonsils out or having, you know, abdominal surgery and then going to the recovery room and vomiting for 2 or 3 hours. And I, I think that one of the things that Heron's done that's really great for this is they've really taken it beyond that immediate acute phase.
Because the worst thing for us as providers and for ASCs and facilities is if we get a patient under control in the phase I or phase II and then send them home, and the second they get in the car, they get halfway home or they get home and start throwing up, all they hear is, "All you cared about was getting me out of your facility, and you didn't care what happened to me when I got home." And that's a huge, huge patient dissatisfaction piece for us. And we all know as providers and as facilities, payment's now tied to satisfaction. So that's a big piece for us.
When I can go to a patient now and say, "Hey, I've got a drug that I can give you one time and get you two days of treatment for postop nausea and vomiting 'cause I care what happens when you get home," it changes the world for them. A lot of the other things you look at from a burden standpoint, like we talked about the unmet need for pain control, I really think it's an unspoken need from a postop nausea standpoint. Like they said, we don't see as anaesthesiologists; we don't wanna hear about a problem we can't take care of.
So I think that what's happened in this is we just have about a 30+% experience with postop nausea that the PACU nurses just don't call us about because they know we've already written every drug we can possibly give them. All we can do is support, hold their hand, and say, "Good luck." So now that thing's changed for us. And when you go to the anaesthesiologist and ask them about postop nausea, they may say, "No, no. My patients don't throw up. We do a great job." Then you walk across the room and go to the PACU nurses and say, "Hey, you got a postop nausea problem?" They said, "Oh, yes.
We have a postop nausea problem." In our center, we have 4 ORs, two procedure rooms, and 4 PACU bays, which means if one of those PACU bays backs up at all, it basically runs our entire morning. So if we have someone that throws up for 30 or 45 minutes, that's gonna back up everything in the OR. And PACU time costs a ton of money, probably $15-$20 a minute. It's expensive a place to be. And it costs a lot of things to have those kinda delays. The other thing is if patients go home and start having nausea, a lot of times they end up back in the ER. For us as an ASC, that's a reportable event to the government.
So if we have someone that goes back to the ED in the first 24 hours, we have to report that back. And if you have a certain number of those in a year, you know, it becomes a big issue, and you have to go under a different review. So there's a lot of things that tie to postop nausea and vomiting beyond just patient satisfaction even. The problem is, what have we done to treat it? There's a lot of different receptors. You'll see that in a couple slides here. But really, this one here, when I saw this one, I think this, this molecule really makes a huge, huge difference as far as where it hits and how it prevents things. It really prevents the vomiting piece very, very well. The oral formulation's been out for quite a while.
But what's crazy is the lack of knowledge about that molecule. I think we've done a really good job so far. I think the company's kinda stepped into that and tried to be working with that education piece and introduce this molecule. I spoke to a group of 16 providers on Monday night. Three of them had never heard of the molecule before. So, you know, by far, the bulk of people don't even know about the molecule, much less this ability to deliver it. Because when we've got an oral formulation in our world, a lot of times, I don't see a patient until three minutes before they go back to the OR. If I'm having to use something oral that's gonna take five hours to take effect, it's borderline irrelevant in my acute care there.
But if I now have a drug that comes in in 5 minutes and has 97% receptor activation and really makes a difference, when I see the patient and the doc and they say, "Doc, I throw up every time I have anaesthesia. Is there anything you can do for me?" I can now with confidence say, "I actually do." I can tell you we've given about 90 doses of this drug in our center, and they're all high-risk patients that we've done because we don't. It's, it's really a selective process. Not one of those patients has thrown up in our center so far. So, this, this drug has made a massive, massive difference for us.
The other thing that I think is changing now when you look at it and everyone if you watch the news and read everything, the Ozempic-like drugs, we know that those GLP-1 agonists and stuff, we know what they're doing for weight loss and everything. What we don't see is what you don't see is what it's doing for anaesthesia. It's making a massive, massive change in how we approach patients in the perioperative period because of the delayed gastric emptying that those patients are experiencing. They're at very high risk for aspiration. The ASA's come out with specific indications about how to manage those patients and how to work through those patients. But the bulk of patients that are on those, a lot of them don't even tell you about it till you walk in the morning of surgery.
So we're really having to take that patient population and treat them even, even more specifically for postop nausea and vomiting. Again, when you look at prevalence, probably 30% of all patients are gonna have some kinda postop nausea and vomiting even if you treat them with our kinda common drugs like Zofran and Decadron and stuff. Those patients that are higher risk and the things you look at, are they female? Are they nonsmoker? Do they have a history of postop nausea and vomiting or motion sickness? And are they gonna get opioids in the perioperative period? Well, you can look at this and understand that probably half your patients are gonna be considered moderate to high risk. And that's really where the art side of our anaesthesia comes in is how many of those 65 million cases a year can we as anaesthesia say, "Okay.
These are the patients that we really feel like adequately meet a criteria to use a drug like this? And it's probably in the, you know, 20 million number there somewhere. About a third of those patients probably deserve to have something like this on the front side. Now, we don't have a treatment indication with this drug yet. But I think that's something that we've had a lot of providers look at and nurses and stuff that explore that too and look at. So I think that as you explore that and we go forward with that, that number could even increase with that. But as you go, if you have two risk factors, you really should use two drugs. If you have three or more, you really should hit multiple receptors and use three or more drugs.
I think that this is, kind of a pictorial representation of the actual consensus guidelines. So this is all the folks that work in the perioperative period that have come together and said, "Okay. What, what can we do to mitigate PONV, and how do we address this as providers in our centers?" You look at the risk factors like we just talked about. There's different things we can do from an anaesthesia standpoint, regional anaesthesia. We don't use nitrous hardly at all anymore because of the nausea piece of that. We look at opioid sparing, which is where we get things like ZYNRELEF that make a huge, huge difference for us from that standpoint. But there are certain things that, that when it comes down to if we've gotta put someone to sleep, we've gotta use general anesthetics, then we have to mitigate the risk for that postop nausea.
And like I said, if they got one or two risk factors, you typically are gonna give a couple agents. That's usually gonna be Zofran and Decadron. When you get to two or more risk factors, that's when you start looking at multiple, three or more agents. And that's really where we add that aprepitant molecule in. And that's where APONVIE comes in and makes a huge, huge difference, I think. From a rescue treatment, that's been probably the biggest space we've had an issue with historically. There's just not a great drug to treat, you know, the rescue piece of that. And hopefully, we'll see some of that change as we continue to get experience with this drug. So this is APONVIE. It's the first and only IV NK1 antagonist for the prevention of postop nausea and vomiting.
Like I said, superior vomiting prevention. So you look at probably almost an 18% improvement on vomiting alone out to 48 hours with this drug versus other drugs. It was rated the most effective single agent. So like I said, we use multimodal approach. But if we did go to single-agent therapy, this would be the one that's been proven to be the most effective. It's great for us as anaesthesia providers. We hate anything that we have to mix and hang and let it sit there for 20 minutes or 30 minutes. This is a drug that we draw up, and we give as soon as we push the drugs. So it's easy for us. It makes sense for us, and it makes our patients very, very happy 'cause, like I said, this gets dropped in our laps all day, every day.
You know, so when they go see the surgeon on postop day two, "How'd you do?" "Well, my knee's great, everything, but I puked for a day and a half." "Oh, that was anaesthesia." "Yeah. Sorry." So we and we're not there to. We don't get to. We don't ever get a chance to say, "That really wasn't us," 'cause it probably was from that standpoint. But I do, and when you look at pricing, this is the only drug that's treated for postop nausea and vomiting that's actually reimbursable by CMS too. So that is a huge, huge piece for these facilities. When you look at the cost of a postop nausea experience, it can be extremely devastating for a facility and for the patient. So, this is something that really makes a huge, huge difference.
So these are three different studies we look at for kinda real-world efficacy. The first one is, aprepitant versus, ondansetron or aprepitant with ondansetron versus ondansetron alone, almost a three a little over a threefold, reduction in vomiting with aprepitant with Decadron, which is something we use we use Decadron for lots of different things, but one of the things it's, it's great for is nausea versus ondansetron, which is Zofran with Decadron alone, still a, a twice as good as what we see with, with those two alone. And then when you look at aprepitant versus, Zofran plus Decadron plus another, a third agent, you still see a markedly, marked improvement in PONV and vomiting and reduction with aprepitant alone. I really, like I said, we've given this drug in, in to lots of folks, and they're all high-risk patients.
When we brought it into our facility, some of the administration was a little hesitant and everything. And I said, "Tell you what. Give us 20 patients, and you pick the 20. You find the 20 patients that you think are the highest-risk patients for stopping your flow, you give them this drug and see what happens." And like I said, those 20 flew through. Not one of them vomited. We're now, you know, like I said, close to 90-100. We still have not had one that vomits. We still have some nausea that we deal with in the PACU. But this drug, I just cannot envision a scenario where this drug is not the cornerstone and standard of care therapy for postop nausea in the next, you know, 18-24 months. It just it's performed that good.
And I think once the education piece reaches out to the Physicians and they understand the molecule and understand what we can provide as Physicians, I, I think it's gonna be really, really hard to not justify giving this to, to the right patient population. Like I said, this is the study they looked at. It was, a little under 600 studies and almost 100,000 patients that showed aprepitant was the single best or most effective molecule, for preventing vomiting out to 24 hours. And I think that really has been replicated and been shown to us clinically and, and continues to push forward with what we've seen, day to day in our practice. So I'm gonna turn it back over to, to Dr. Werner here and let him discuss the ERAS protocols and everything from there.
Thank you, Dr. Robbins. Excellent. So just to give you guys a brief view here of what it looks like on an institutional level, hit all the high points there. I do wanna mention one thing. The name APONVIE is wonderful. So these drug companies making these, it's an acronym. It's aprepitant for postoperative nausea vomiting injectable emulsion. So PONV is actually in the name, so it's easy for people to remember. So one of the best names I've ever seen for a pharma drug. Just note that. But looking at it from a P&T perspective, we're always weighing the pros and the cons here. And you heard all the pros already, the benefits, the efficacy of it, the single most effective agent. But again, with this piece, sometimes it gets overlooked, that 48-hour duration.
So all of our other antiemetics that we typically use, they work for 6 hours, 8 hours. So again, that patient's out of sight but not out of mind. We're still managing that PONV, hopefully not having a readmission to the for a complication. On the con side, with anything, we would look at it. We'd evaluate it. Cost becomes a con section just when you look at comparables 'cause we're in a, a generic market for PONV prophylaxis or vomiting treatment per se. So those drugs cost pennies, Zofran, dexamethasone. So it becomes a con here. But as he pointed out, it is reimbursable currently, has that same pass-through status that ZYNRELEF does. So it's reimbursed outside of that surgical bundle. Overall, not a high-cost drug, about $58 a dose.
So for the impact it can have when we're evaluating it, cost-efficacy, one episode of PONV is noted to cost about $1,000 to your institution between the length of stay, rescue antiemetics, cleanup on aisle five, all those pieces that go into vomiting when that does occur. So drug interactions, it has a couple drug interactions that we're mindful of but things that we can educate around, not really problematic there. So, you know, basic formulary add. They're gonna add it for that moderate to high-risk patient population, those patients that have those risk factors, which is pretty easy. About half of our surgical population ends up in that high-risk portfolio. So these patients, putting this in as the foundation, as that third agent, one of the biggest things that I always point out is the safety profile of this, the antiemetics that we have.
They have a lot of overlapping side effects, and they become additive for our patients. So when we looked at the guidelines that Dr. Robbins showed, he said, "We need to give three agents to these high-risk patients." That becomes a safety risk for our patient. APONVIE doesn't have those common side effects, does not share those side effect profiles. So it makes it that nice piece, that nice foundation to our PONV prophylaxis. So to wrap up this section here, so we got two new foundational elements for our enhanced recovery after surgery protocols really impacting our patients. Me personally, I would not go have surgery somewhere if I couldn't receive both of these products if it was a major surgery. So looking at ZYNRELEF, we got some tailwinds coming for ZYNRELEF. So the significant label expansion, that just happened in January.
It takes time for these things to evolve after that label expansion so formularies can re-review it, what the label now includes, how they can adopt it. It's more than just more indicated procedures and more providers, possibly more champions bring it into institutions but also allowing these institutions to now substitute, not have multiple products on their shelf for various disease states but have one product that can be utilized many places. So now with the broad label essentially being all soft tissue and orthopedic procedures, it allows for that formulary adoption or substitution for a wholehearted switch. The CrossLink partnership, this is awareness. You're gonna hear a lot of it about it today. But it's awareness. It's boots on the ground. It's education. So a lot of people don't know what ZYNRELEF is yet. So it's not their foundation of multimodal analgesia.
But as they get educated, as we get those contacts, and they learn about the product, and you see the clinical impacts and outcomes and impact, we're gonna see it become that standard of care. So opioid stewardship, we all turn on Netflix or the news, and we see opioid story after opioid story. We lost 110,000 patients, 110,000 people in America last year. So it continues to be a problem, and will continue to do be a problem until we, we change the paradigm, right? And ZYNRELEF is one step in changing that paradigm. But we have our major accrediting bodies pushing us along also saying, "What are you doing for the opioid epidemic? What are you doing for that problem? Do you have an opioid stewardship program, and what do you provide for your patients?" So to be accredited now, you need to participate in these impactful elements.
The opioid settlement, as you're aware, Big Pharma got slapped these settlement funds. $53 billion was just distributed throughout the United States. That has to be spent on awareness, treatment, and prevention. So more awareness around products like ZYNRELEF or opioid alternatives, if you will. And finally, we have the NOPAIN Act. That's coming in 2025, Q1. And what that's designed to do is provide reimbursement for non-opioid products that are proven to reduce opioid consumption. ZYNRELEF obviously qualifies for that. ZYNRELEF is already reimbursed, but this will continue to provide reimbursement for ZYNRELEF. All the way through 2027, it's planned, and we expect that to continue on. I don't believe the government will back off a program like this.
Once it's out there and they're providing that reimbursement, I don't think they're gonna revert back and say, "We're no longer gonna provide coverage for non-opioids." So it's also gonna bring along the commercial payers. They typically follow CMS, and they wanna be on the right side of that fence also. So more and more commercial payers will be providing this reimbursement outside of our bundles, making this an economic advantage to include ZYNRELEF and get the clinical impacts at the same time. For PONV, it's really education and awareness. So you've seen it's a, a best-in-class agent, number one most effective antiemetic there is. It's the only long-acting agent. It suits itself to that perioperative space for our primary users, for anaesthesia with APONVIE. So the PONV guidelines, there's a new update coming. So likely, we'll be able to get a, a name mention in there.
That'll really boost the awareness. But otherwise, it's out there telling the story, showing the impact that this can have for patients. Finally, it's the GLP-1 epidemic, if you wanna call it. They estimate about 10% of our population is gonna be on a GLP-1. So that's pretty wild to think about those numbers. 10% of the patients are on the Wegovy, Ozempic, utilizing GLP-1s. But as Dr. Robbins said, these are high-risk patients because of that decreased transit time, their higher risk of aspiration and complications. So they're automatically in that group that needs three agents on board. And they're also continued risk. So having something that's 48 hours, you could basically blanket, say, all these patients, they should probably be getting APONVIE for the surgical procedure.
Oral's not an option for these patients 'cause we're seeing the complications with other oral medications in these GLP-1 users because they don't absorb medications like a normal patient with normal GI transit. So big population there, big numbers of patients that would likely benefit from APONVIE. So two foundations for us for postop pain and postop nausea vomiting, true game changers. And we're, we're shifting that paradigm to these become the standard of care. So we're gonna open up for some, some Q&A from the, the group here, for Dr. Rechter, Dr. Robbins. Any questions?
Hi, Brandon Folkes from Rodman & Renshaw. Maybe just a question for I think it's Dr. Rechter. You talked about the new technique that it's changed a lot. Is that changing the amount of ZYNRELEF you're putting into the patient?
It, it hasn't changed that, actually. It's just really from a delivery standpoint, it just made it so much easier 'cause the one thing when you're dealing with surgeons, number one, the guy's very good, hopefully, because he's done it so many times. And the one thing which you're always saying, "Don't change what you do. You're good at what you do 'cause you've done it a million times, and you do it this way and whatever." So the whole key is this is something that's done normally at a step where we normally would put in some type of a local anesthetic. So as he mentioned, we were doing before they had ZYNRELEF, we had these in other injectables where we'd inject these all around that area. So we would implant, let's say, wash before we close, and then we start closing.
But that's the point we're putting in our local anesthetics to try to give them some relief when they're, you know, for the postop period. For us, we're trying to get them home. You know, we really want them to get out of the hospital. So we want something that's gonna work like that. So the timing was perfect. We were putting it in just like we always had before, but it didn't really change the amount 'cause if you think about it, it's weird. The guy comes into the office with a really swollen knee, and you stick a needle in there, you could drop 150 ccs, and you go, "Well, what's 14 ccs?" 'cause that's what the big dose is gonna do. It works. You get it in there. That 14 spreads around and coats the entire inside of the joint.
You're still putting the same amount of product that's in there. You're just putting it through a much smaller window, and letting it do its thing once it's been placed.
Thanks. Carl Byrnes from Northland Capital Markets. You, you talked a bit about the efficacy gap. I'm wondering if you could also expand a little bit on how much time you think you save in the OR with respect to infiltration of ZYNRELEF versus Exparel in terms of injections there and how might that improve with the VAN and the pre-filled syringe down the road? Thanks.
So it's really, it's a great question. You know, the Exparel, again, when we had products that were going for 6, 8 hours, we said, "Hey, we got something now that's gonna maybe go day, day and a half." We were happy with that. We didn't know that we had a we had a, a 72-hour window to cover. So maybe the discussion was, "Hey, listen, you're gonna get out of here and say, 'I feel pretty good.'" I'm like, "Yeah, you do 'cause you got this medicine working. But what's gonna happen to you is tomorrow afternoon sometime, it's probably gonna come alive." So we would always kind of get them ready for that.
So then all of a sudden, we had ZYNRELEF, and we said, "Hey, we're gonna put this in, and its place anyway." This basically didn't add any more time 'cause remember, it really was changing what we were doing. At the time, they called it Rex Solutions, but everyone had some injectable that they were putting in there anyway. So the Rex Solutions were like 300 ml. So these big syringes with big needles, and you're trying to squeeze it all around the femur and the tibia and here and whatever. So it was taking about the same amount of time to put that in and then to put the ZYNRELEF in.
Now, the little window technique, I mean, when we first were doing the trial, we were really focusing on, "Make sure you get it here and get it there." And we found out we don't need to do that. So if anything, it's been a little bit quicker using it in the technique that we're doing now. And you can imagine in the OR, every minute, it's super expensive. So that really helps to kinda get it in there and let it do its thing. And again, from an effectiveness standpoint, then it's really taken it to the next level, and it's been so effective for three days that for me, again, everything, hips, knees, shoulders, you get a shoulder replacement. People used to stay in the hospital four or five days. Now, people are going home the same day.
But finally, if I can get them on the backside of the inflammatory phase, they really come to the office in a totally different state. In fact, one thing which we saw, this was anecdotal. But when we have patients that were coming during the trial period, we had patients that were in trial and people that weren't. So the people that were in the trial, we'd walk into the room. The guy would be moving his knee like crazy. And that's important when you have a knee replacement. Hips are a little bit easier. You know what we say? It's very technical for the doctor but easier for the patient. Knees, they're not that hard to put in, but they're hard for the patient. The incision's in a terrible spot. Nobody wants to bend it.
But if you can get their pain under control and the fear factor, they just don't wanna bend it. They start moving it like crazy. So we were seeing from a motion standpoint, I could tell who was in the trial and who was getting the product and who wasn't based on motion alone. So it just had so many benefits that we saw that were after the fact.
Good morning. Serge Belanger from Needham & Company. Dr. Rechter, with the implementation of the NOPAIN Act starting in 2025, do you expect that'll lead to a significant change in how you use ZYNRELEF or Exparel across the board since it'll kinda simplify and broaden the reimbursement of these products?
So the fact that it's got reimbursement now is terrific. But, you know, really, it's my opinion, there's no reason why you wouldn't wanna use a product like this in any area that you're gonna use a local anesthetic. I mean, if you think about it, again, from what we talked about from the science behind it, I mean, even if a guy that gets a laceration in their knee, they come to the emergency room, they got a big cut, they're gonna get bupivacaine, which is fine, for four hours. Then they get home, their stitches, they start getting swelling in the area. With the swelling, it gets more painful. The local wears off. So what do they do? They have to resort to the opioid medication. So of course, I think in areas like that, it'll get adopted more and more. The reimbursement part's terrific.
I mean, at that point right now, then it lets people trial it. But if you think about it, what it's been doing is we've seen the number one spend in all these hospital systems outside chemotherapeutic drugs was, was basically liposomal. It was an Exparel product. So it was super expensive. So now you've got something that, number one, it's less expensive than that for sure. And right now, it can potentially be free depending on the setting of it. But I do think that it may encourage more hospital systems then to say, "Hey, listen, we wanna try this thing anyway." First, we know that we've got it till 2027. And probably, as they were saying from the NOPAIN Act, that it'll probably go on even beyond that. So I think it may incentivize some of these systems to, to start thinking, "Let's try it.
Let's see what it's all about." So probably so.
Any other questions? All right. Great, great questions. Appreciate everyone's time. I'm now gonna turn it over to Dr. Bill Forbes, our Chief Development Officer.
Thank you.
Thank you, gentlemen.
I get the fun part. First of all, I'm the only thing standing between you and break. So, I'm gonna cover some ground here. I wanna thank Craig for the introduction earlier. You know, I was thinking the other day, I think Craig and I met for the first time in 2011. I get this question all the time from internal employees. They're like, "How did you and Craig meet?" And when I answered, I go, "We met on a basketball court." And they look at me, and they go, "What were you doing on a basketball court?" Well, that's one of life's great mysteries. So I'm gonna zoom forward to May of last year. And May of last year, when I met Craig, I knew he was the type of CEO I wanted to work for.
But it didn't come together until May of last year when we started talking. June is when I was hired. But there were a number of things that Craig wanted to accomplish in R&D. So we started having that discussion. You know, one of the things was cost-cutting. So, you know, it was we have objectives that we need to obtain or achieve, but I need you to cut the cost because there's too much bleeding coming from R&D. And I said, "Well, I don't know if you've looked at my resume, but I'm not really known to cost, you know, cut costs. I'm actually. I've had a CFO tell me that I'm the enemy of EBITDA." So, he said, "Don't worry about it.
I've got this great CFO coming in, and you're gonna love her because she's gonna help you cut costs and income zero. We achieved it. I think you saw on an earlier slide where Craig had mentioned R&D cost, and cuts, we were able to achieve that. But we also had to press forward on a number of other things. This slide actually highlights for you all the four compounds that are marketed at Heron. You know, as you can see, you know, Heron first got SUSTOL approved in 2016, CINVANTI in 2017, and then ZYNRELEF is coming in at 2021. There's been three approvals for ZYNRELEF , as you know. One of the things that he needed, in June of last year is he needed to make sure that we got that sNDA approved.
Now, Craig gave me a whole four months to do that, which I thought was a little unreasonable. And apparently, the FDA did too. That was actually already submitted by the time I show up. We had a delay, but it ends up getting approved in January. So that completed the development work on ZYNRELEF . And we're gonna talk a little bit more about ZYNRELEF. Obviously, APONVIE, as Craig alluded to earlier, comes in in September of 2022. So let's talk a little bit about what needed to be done. The sNDA in January, the VAN, the Vial Access Needle was the other thing that was on the trajectory to get finished up. And there's a reason why we wanted to get the VAN in. Let me pause a little bit here and just kinda go through this.
The current marketed presentation of ZYNRELEF uses a vented vial spike. That vented vial spike is a 510(k) approved Class II device. You can purchase this off on the market. So that vented vial spike is sterile. Unfortunately, the vial itself that contains the ZYNRELEF is not sterile. So this bridging of sterile and unsterile is it presents a preparation hurdle for ZYNRELEF. Now, you've heard very clearly from Dr. Rechter that once the product is in the surgeon's hands or in the PA's hands, they can administer it quickly and very effectively. So it's not a problem for the surgeons and the administration of the product, but the preparation is a hurdle. Because this is a combination device, it's drug and device, the problem that we run into is that there needs to be multiple professionals involved in the preparation of it.
On the left is the Vial Access Needle. One of the things that the company has done is designed and manufactured and tested this device. So Heron, being a drug company and a device company, now we're talking about setting up the device portion of this and advancing it in a way that it can be used more smoothly in the operating room. So I'm gonna start first with one of the problems, which is the rate of withdrawal of the product from the vial. And this is data that's on the left from the Vented Vial Spike. And as you can see, the rate at which this is actually able to be withdrawn is a product of temperature. So as you increase the temperature, you can actually withdraw it. So 25 degrees Celsius is approximately 77 degrees.
We actually oftentimes warm the product to temperatures higher than that in the operating room to allow for faster withdrawal. So the vented vial spike, when the original submission went in, this is the data from that. If you look on the right, this is the VAN data that we're about, you know, that will be submitted with the submission that will go in here shortly. It's not submitted yet, but will be imminently. If I draw your attention to the 200 mg bupivacaine 6 mg row of meloxicam and also the 412, these are the two doses that are used most commonly. And as you can if you look across and you see where the VAN is on these two rows, you can see that the 206 can be drawn in about 18 seconds, whereas if you use the current marketed vented vial spike, you're talking about 106.
And if you look at the 412, it you'll see that the VVS is 186 seconds versus 45. Obviously, it's about approximately twice as much because you're drawing twice as much, from the 200 to the 400. So speed of withdrawal is, is one of the big hurdles that we needed to. It's part of the design of the VAN itself. So when the VAN is designed, it has to fulfill much of the 510(k) requirements, biocompatibility, and E&L testing and things of this sort. So all of that work had to be done and overseen by Heron itself. And so that was part of the solution. The other part was ease of, of preparation. And I'm gonna draw your attention to the top left corner here.
If you look at the VVS instructions for use, you can see that the non-sterile nurse actually has 5 different things that he or she needs to do in this presentation of the current marketed. So and as you can see from the diagrams down below, if you actually look at diagram number 6, I believe it is, you can see that at one point in time, both the sterile and the non-sterile technician are handling this product. So this is the VVS presentation. This is the VAN presentation. You see where the number of steps that are involved with the non-sterile person has gone down to essentially two. What we're doing here is we're essentially just having them open the packaging and drop the non-sterile vial into the sterile VAN itself.
At that point in time, all of the work is conducted in the sterile field by that nurse or technician. So this was the hurdle that we needed to solve and wanted to solve. And that's why we've been doing it. Many people ask us, "Why did it take a year to actually accomplish this?" It's because, as I said before, this is a case of us actually, you know, designing, manufacturing, and testing this entire process ourselves. Whereas many times with a 510(k) device, just like with the VVS, you're just taking it off the shelf, and you're relying on that testing. Here's a picture of the manufacturing, which obviously, we use contract manufacturing. And then the VAN kit. As I mentioned, during the break, one of the things that you'll be able to do is, actually touch and feel the VAN kits.
They're out there for you to take a look at so you can get a closer look at it. And this has been mentioned before, but, you know, obviously, the ultimate solution to all of this is to take preparation of the product out. And one of the initiatives that we have, obviously, filing the VAN, getting that approved by the end of this year, and getting it launched by the end of this year. But with the prefilled syringe, it's gonna take a little bit longer to do this. And we're, we've got an initiative on this going right now. Our hope is that we have the prefilled syringe by the end of 2026. So with that, I'm just gonna pause. And, I think we'll just go to break. All right. Thank you.
Welcome back, everybody. Obviously, thank you for the attention this morning. Hopefully, you get a sense for why we're so optimistic and excited about what we can do at Heron. For the rest of the day, you're going to see how we view the business opportunity in front of us. I think reflecting back to the past 6-9 months as we have been building this team, making some really important decisions related to the organization on how we move forward, I think we'll look back and see this as a foundational moment for our growth. For the rest of the day, you're going to hear a lot of the experts who are leading the various business units. We're going to start on the acute care franchise. But first, I wanted to give you a bit of a view as to how we look at the market.
You've seen and heard a couple of different numbers thrown at you today. But the one thing that we are for sure confident in is the 65 million procedures done in the U.S. annually. So obviously, that's growing about 1% year-over-year. But the way that we break down the acute care franchise and the business opportunity is, and you heard from Dr. Robbins earlier, about half of these procedures, the patients are at high risk for PONV. So 32.5 million is our patient opportunity in front of us. And that's how we're assessing performance and our success moving forward, is how many of these procedures are getting treated prophylactically with APONVIE. On the ZYNRELEF side, the new label expansion in January almost doubled our opportunity. So the label prior to January 23rd, we had access within our indication to about 6-7 million procedures.
With the expanded opportunity and the PDUFA date of January 23rd and FDA approval, that almost doubled that opportunity to 13 million procedures. So we're going to talk to you a little bit about APONVIE, first setting it up in terms of our strategy and guidance here. A lot of what Dr. Robbins spoke about was those patients at high risk. And one of the things that we learned as we launched and started talking about APONVIE to various institutions is there were certain surgical lines that were more receptive to the burden. And so as Dr. Robbins mentioned, in terms of talking to the PACU nurses, talking to the above-the-waist target surgical procedures - bariatric, ENT, neuro, and plastics - these are all specialties that if there's an episode of PONV, it really affects patient outcomes negatively. So we really are hyper-targeted there.
In terms of our strategy and focus, it doesn't end there. So this is very much an enter through that target audience and expand within the institutional setting. So again, as Dr. Robbins mentioned, what happens is we get early experience across one of these surgical lines, let's call it bariatrics, for instance, it starts to spread a little bit through the PACU, and people start asking questions about, "What are you using on that surgical line on those patients to prevent nausea and vomiting?" And then every surgical line starts to adopt. So we're excited about how this can kind of snowball over time. On the right side, you're looking at that higher-risk number, again, 50% of the overall procedures, and just hypothetical procedure shares over time. If we were to achieve 1% share, that's 325,000 procedures.
At $44 net price, you're looking at $14.3 million in net sales. So again, a small portion of business can really generate a high volume of revenue for us. And as David's going to talk about, we have specific objectives that are sort of driving to peak share within an institution is around 20%. So this is just getting started. As I mentioned, we've just started to build the foundation for these products. But I'll turn it over to David to talk a little bit more detail on how we're going to make this happen.
Thank you, Ryan. So what I'm going to do today over the course of the next 15-20 minutes is provide you an update from a performance standpoint for both A PONVIE and ZYNRELEF. We'll talk about the opportunity that we think we have in front of us.
Then I'm going to close with a progress update around CrossLink and why we're optimistic and excited about the partnership. I do want to introduce Thomas Fleetwood as the CEO for CrossLink. Thank you for being here today to answer questions and also add some comments. Turning our attention to APONVIE, if I can get you to look to the right-hand side. As Craig mentioned, one of the first things upon being elevated to the VP of Sales in September was I recognized that there was a gap with APONVIE. The gap kind of consisted of it was twofold, right? From a clinical standpoint, I was hearing from our sales representatives that they didn't really feel like they had the confidence and knowledge to sell this product effectively like they wanted to.
The second challenge that we had was I definitely think we didn't put the right emphasis or focus around APONVIE coming out of the launch. We were so focused on ZYNRELEF that we really didn't prioritize the right behaviors from our sales Reps. So two of the things that we did quickly to turn this around was we'd put together a robust training program where we ran POA meetings in October that really focused on the ability to create the burden of cost of an episode of PONV. So we increased our Reps' clinical acumen, which increased their confidence and allowed them to go head-to-head versus anaesthesia, directors of pharmacy, and institution to share why there was a need for APONVIE.
The second thing we did was we really incentivized and pushed our representatives to get more P&T submissions because we understand and know that in a hospital institution, if you don't have formulary wins, product 99% of the time can't get used. So we really incentivized the right behaviors to drive performance. As you can see, over the course of the last six months, seven months, you see significant growth on the right-hand side. I attribute that to, obviously, our refocus of the product on PONV and putting the right rewards in place. As we move our attention to the left-hand side, you'll look at it from a quarter-over-quarter basis. In Q1, we grew by 53% compared to Q4. So we're starting to get that traction, and it's just the beginning.
What I can tell you is with one month of data here in April, you'll see that we did 6,660 units. We're on track and confident to do more than 20,000 units in Q2, which would be another 50% growth for APONVIE. So why are we optimistic? You can see that with the focus since Q4, we've had more than 109 formulary wins since that date. In the first quarter of Q1, we had 35 new health system wins. To date, we have 305 ordering accounts. Our goal is to continue to fill this pipeline because we do know it takes about three to four months before accounts come online once they're approved. So how do we measure performance today and look at the opportunity in the future?
We tier our hospitals either Tier 1, 2, or 3 based on the procedural count within each individual hospital. As you heard from Ryan, there's 65 million annual procedures. But our really opportunity is 50% of those patients for that high-risk patient portfolio. So within our current ordering 305 accounts, we have 31 individual hospitals or clinics that the opportunity is 887,000 patients. Now, our goal internally, driving to peak performance is we should own at least 20% of that market. Now, some are going to do more. Some are going to do less. But we're confident that we can get at least 20%. So when we look at these instances and we look at the high performers, if we get our 20% market share, which is driving to peak performance in our high Tier 1 targets, that is worth $7.8 million.
Looking at our medium-sized hospitals, 64 of them fall into that bucket. There's a potential for 640,000 procedures annually. 20% of that is 127,000, which is an additional $5 million. Obviously, for the low, we can do the same thing, and that adds another $1.7 million. In totality, today, with just 305 accounts, we believe and know or are confident that we will get 345,000 patients, which will generate $15 million in revenue. If we really look at the opportunity, there's 12,000 ASCs in hospitals throughout the United States. Of the 32 million, we already have 1.7 million that we currently are kind of fishing in that pond. But there's another almost 31 million patients that are out there. Our goal is to get 20%. The potential for this product could be $270 million.
So I wanted to give you an example of looking at a hospital system that has made the decision to fully adopt it, right? We talked about earlier that 20% is our internal goal. But I think as more and more exposure and more and more hospitals and anaesthesiologists start using this product, I think we're going to have more instances where people will fully adopt APONVIE as part of their protocol. So this is a hospital system that has made a decision to bring APONVIE in and fully adopt it. They have 7 campuses, do roughly 50,000 procedures on annual basis. The high-risk patients account for almost 25,000 patients. How do we know that this account has fully adopted it? On average, there's 2,070 patients on a monthly basis. Now, I think it's important to notice that this just didn't happen from a P&T approval.
It took some time. So this account actually approved product in August. It took about 3 or 4 months to get buildup into the CPOE and the Epic system. There was also education that needed to be taken place and also protocols that needed to be implemented. So it wasn't until December that they started placing their first order. And you can see over the last 5 months, they have continued to adopt APONVIE. Today, again, we talk about 2,000 being fully adopted. They're doing 1,900. So this is an example of a hospital fully adopting it and the potential to herein into APONVIE. This would be a $1 million account. To give you an example of how things ramp up, obviously, on the right-hand side, you'll see that this is the previous slide that we had where an entire system, 7 hospitals, decide to adopt APONVIE.
But on the right-hand side, we just wanted to give you an example of two different individual accounts. So you'll see it's not like just turning a water spigot on. But what happens is over time, and especially once you get to the five- six-month period, you can see how it starts to ramp up. And we're starting to see this happen in a lot of our other accounts as well.
Thank you, David. So quickly transitioning to ZYNRELEF, similar to APONVIE, we talk about an enter and expand approach with this product. I think one of the things I observed quickly when I joined the organization in August, we're blessed with a broad label that got broader in January. That can be a blessing and a curse from an execution standpoint, right?
Because you have to make decisions strategically on where you can actually win and where you can own a space. Clearly, what you're learning from us today is that our focus in 2024 is on ortho, right? And so we plan to go in and own the orthopedic procedure space. We have a high success rate there, higher volume of units, and then higher cases per procedure. So one of the things that we're going to talk about a lot today is how we're going to enter and expand, driving ZYNRELEF volume within orthopedic procedures with our partnership with CrossLink, which David is going to talk a lot about. On the right side, you see how we view the market opportunity. So originally, I set this up with the 13 million procedures that were indicated for within our label out of those 65 million.
If you drill down the individual procedure types and you just focus your attention to the top two, which are the sNDA expansion, spine and shoulder, as well as hip and knee, which we already had the indication for, you're looking at just over 3 million procedures within ortho. So when we assess our execution and our performance and how well are we doing, are we achieving success, these are the numbers that we're looking at. And we're looking at that $3+ million opportunity within ortho or million patient opportunity. You correlate that to using a blended net price of $184, $558 million opportunity within orthopedic procedures alone. Expand that to all indicated procedures, all ZYNRELEF indications, you're upwards of a positive of $2.3 billion.
So you can see where our optimism comes from and just the foundational footprint that we're making and the steps and the decisions we've made over the past 6 to 9 months to build from here. So with that, I'll turn it back over to David to talk a little bit more about how we're going to do t his.
Awesome. Thank you. All right. So at first, I want to just want to go over performance. Apologize about that. If you look at the top left-hand side, you'll see month-over-month demand, quarter-month-over-month demand. So if you look at Q1 2024, we did 29,600 units. In Q4 of 2023, we did 29,829. So obviously, it's flat. We're not happy with that. But I do think it's important to realize that in Q1, there is seasonality to elective procedures.
So typically or historically, there is a 16%-20% drop in procedures. So I'm ecstatic that we were able to maintain that business and not see that drop with ZYNRELEF. When we look at it on an annualized basis, Q1 2024 versus Q3, from a demand standpoint, we grew 30%. But from a net revenue standpoint, we grew 43%. Down at the bottom, you'll see our month-over-month since inception. And one of the things that we realized when we started talking with CrossLink or why we started with CrossLink was that we have 47 Reps out in the field. We have a little bit of a bandwidth issue. You guys obviously heard about the preparation. We need to be in those cases on a regular basis. So with 47 Reps, the ability to continue to expand becomes a challenge.
And that's why we know that the partnership with CrossLink is really going to help us increase our trajectory because they're in those cases every single day. And I'll have Thomas share some words here in a couple of minutes. So that leads me to our partnership with CrossLink. So we signed the contract on January 7th, 2024. Since then, we've been extremely busy. January, we really had to build out a robust training program specific to CrossLink. In February, we launched our online training platform to the joint team for CrossLink, which has 150 Reps. They completed that training in February, which led us to then doing five in-person trainings. And we're talking about roughly 30-40 individuals at each site. We did that in March. And then that joint team actually went live April 1st. And I'll talk about their success that they've been having to date.
Since then, they do have two co-leads. Those co-leads have been actively working to add regional distributors outside of the legacy state for CrossLink, which is North Carolina, South Carolina, and Georgia. In the month of April and May, we have already started training and implementing the distribution across the country, which I'll share with you on a few other slides. Over the next several months, I can tell you that we will continue probably two to three training classes on a weekly basis on onboarding additional regional distributors. One of the things that we have to do and we are doing is it has to be strategic. It has to be methodical. It has to be precise. We want to ensure that we keep and have the onus on the training.
So the live training is actually conducted by us in person at the different sites across the country. To give you an example of what the training looks like, on the left-hand side, you'll see what the individual, what I'll call Med Reps, go through. So they go through 10 hours of training focused on five different sort of buckets. The first one is MOA. Second is core message. Third is prep and administration. Fourth is the ability to handle the anaesthesia questions and conversations. And then obviously, the last one is compliance. After that, we schedule in-person training. To the right-hand side, you'll see individuals come in. And we facilitate a very didactic training.
One of the things that we do while we're there is we want to ensure that we arm them with the ability to leave this training and be able to have the confidence to go out with their customers and engage in conversations, not only just with the Physicians but also with the institutions. We have a very robust training and it has gone exceptionally well. When looking at the implementation and how it continues to progress from a CrossLink standpoint, I can tell you that this is changing on a daily and weekly basis. Currently, phase I was the CrossLink team. We have trained 150 joint Reps. About a week ago, we finished training their trauma team. The joint team has been live since April 1st. I would say the trauma team is live as of potentially last week.
That was phase I. While we completed phase I, our co-leads were also helping us move into phase II, which is adding regional distributors, which are in green. We had 11 signed. We're up to 16 contracts regionally signed. It's over 200 Reps. In the states of Michigan, Kansas City, St. Louis, Dallas, and Houston, we've actually trained those Med Reps live. And they're actually actively engaging customers today. And then phase III, which is the yellow, we're starting to schedule those trainings as we're moving forward. I think we're already booked out into the June time frame. And then finally, our goal by the end of the year will be to have a regional distributor in all 50 states and have the bandwidth and coverage that CrossLink can provide us. Anything you want to say?
So I'm Thomas Fleetwood. I represent CrossLink. We are oh, sorry. Excuse me. So my name's Thomas Fleetwood. And I represent CrossLink. This is our 46th year in business. And we're the largest private orthopedic distributor in the United States. We are super excited to partner with Heron and the team here. Incredible opportunity. The training so far has gone amazing. We work with a lot of different companies. And the Heron team and the training they've set up has literally gone off perfect.
Our guys are literally just starting to hunt right now. We're just starting to get cranked up. And we're building out across the United States. So a lot more to come. The response so far has been fantastic. It was interesting. We were doing our due diligence on the product. I hosted a meeting, a roundtable of what I would call 1%ers. It was a group of surgeons that are super high volume.
We were doing a roundtable on a number of topics. But one of them, obviously, was post-op pain control. And one of the questions asked was, "Was anyone currently using ZYNRELEF?" And the answer, show of hands, was zero. And my next question was, "Has anybody heard of ZYNRELEF?" And no show of hands. So I knew we had a winner. And I knew that there was a huge opportunity here. The response, again, that we've seen has been fantastic and is just getting sta rted.
Awesome. Thank you, Thomas. So when we look at the early impact that CrossLink is having, I am only using April's month and using the states of North Carolina, South Carolina, and Georgia. So traditionally, we as an acute care sales force, we're adding about 10 Orthopedic Surgeons across the country on a monthly basis.
In one short month, the 150 Reps have brought 20 new Orthopedic Surgeons that are using product today. When we look at the growth outside of the CrossLink representatives in North Carolina, South Carolina, and Georgia, the territories, 41 of them grew by 3 units in the month of April. In the 6 territories that I have in those three states, they grew by 36 units, which is a 12-fold increase. And we were just scratching the surface.
The other impact that they've had in a short period of time, we're talking 5 or 6 weeks, they've actually introduced us to 180 new unique interactions, whether it be Surgeons, Orthos, Physician Assistants. But we've had 180 unique interactions. We expect to have 80 additional users in the next 30-45 days. That would have taken us 8 months on our own if we could have gotten there. We've hosted 80 programs and in-services or clinical touches.
Hey, David, one thing. I think it's important that everybody here understands the difference between a Pharma Rep and a Device Rep. The magic of the program is a Pharma Rep is most of the time on the outside looking in, trying to get an appointment, trying to meet with a Physician, knocking on doors, trying to get a window to tell them about their product. A Device Rep, in most cases or a lot of cases, has been working with a Physician or institution for maybe five, 10, 15, 20, 25, in some cases, 30 years. Our guys live in the OR. They make their living behind the red line. They're there every day. That's what they do. They wake up and go to the hospital.
And so the interaction, the relationships they have with their surgeon customers is a completely different animal than pharma sales. So when we looked at this opportunity, I think it's important you guys know from the viewpoint we looked at is Heron had 47 Reps in the U.S. And we're going to put a ton of Reps that live behind the red line on the street. I just put my team on the street this past month. And that 20, that was literally like it wasn't even a full month. And we're just getting cranked up. So it's going to be really strong.
Yeah. And to add to that, I think I'll give you one example without naming names. But in the state of South Carolina, our Representative who has probably got 25 years of experience in hospital sales, for two and a half years, couldn't get in front of three Physicians. In less than a week, not only did she get in front of that Physician due to the partnership, those three Physicians are using product today. That would never have happened.
Yeah. And one other thing I'll add is Physicians are incredibly passionate about the implants they use. He mentioned metal. But a lot of times, it's metal and plastic. And they're very passionate about their procedure, what they've trained on, and what they use. And a lot of times, it's very hard for someone to switch between implant manufacturers because they're just used to their technique. Post-op pain control is an issue everybody's dealing with. And I can tell you from the interactions I've had with a number of Physicians, great friends of mine, this is a pretty easy switch. And everybody's very excited about it.
So 2024 is going to be our focus is around Orthopaedics and getting CrossLink up to speed across the nation. We believe that we will more than double the amount of Orthopaedic Surgeons that we have using today. And that is going to be the focus for 2024. What the partnership also lets us do as we move into 2025, it is going to free up our Reps' time to be able to go sell in other procedures and surgeries such as bariatrics, general surgeons. But in 2024, our focus will be around orthopedics, ensuring that CrossLink is up and running. And just to give you a little perspective, this is on average.
But each Orthopedic Surgeon could be worth roughly $50,000 to the bottom line. So keys to success for APONVIE, we'll continue to fill the pipeline with P&Ts by establishing the unmet clinical need and the cost of burden. As you heard before, we'll leverage the Cochrane meta-analysis, which says that aprepitant is the number one agent for postoperative nausea and vomiting. And then we will make sure that we continue, once it gets approved, we can't stop there, right? It's the in-servicing. It's the pull-through. It's the education and also providing that feedback loop that Dr. Robbins has been able to do and see at his institution. From the ZYNRELEF side, we will own and dominate the total joint market. We will capitalize on the new broad label as CrossLink will free our time up to focus on additional procedures.
Then for the rest of the year, it's really ensuring that we do our part to help build out the partnership, be supportive, and roll this out across the country to really see the fruits of its labor in the second half. We will own the perioperative space. That's one of our missions on the acute care side. We remind our representatives that we do have the best-in-class one-two punch and best two products in this space.
So the future is extremely bright, as I shared with you. You've heard earlier that pain and postoperative nausea and vomiting are the two biggest concerns when it comes to procedures. As you've seen, APONVIE is growing steady. We'll continue to fill the pipeline with future P&Ts. The adoption is just continuing to grow month-over-month. CrossLink will help us grow across the country. We'll free up our time. The VAN will help shorten the preparation and bridge the gap to the future, which is the prefilled syringe. So with that, I think I'll pass it to Rob.
Thanks, David. So I'm going to pivot us now to our oncology portfolio and brands. Before I get started there, I think one of the things I really love about our portfolio is just how much the brands complement each other. You heard a lot so far this morning about PONV and pain. Well, what you're going to hear in this next section is about chemo-induced nausea and vomiting and how CINVANTI and SUSTOL play a key role in that treatment.
So I think one of the important things with cancer care, I think everyone in this room in some way, shape, or form has been affected, whether it's a family member or personally, by cancer care. Chemotherapy continues to be the backbone of the treatment of cancer. Even though there's been a number of developments since, chemotherapy continues to be the backbone. With chemotherapy, there are a number of side effects.
And so one of the side effects, of course, is chemo-induced nausea and vomiting. Patients fear that. They fear hair loss, infection, all of those various different things as they're going through treatment. But when you think about chemo-induced nausea and vomiting, without CINV being under control, patients really risk the dose reductions. It affects their quality of life. And we really have two great brands that are complementary to each other that really help patients through that journey.
So I want to take you through a few of the business highlights. I want to talk a little bit about what the market opportunity is, really what the consistency of the CINV brands and portfolio has been over time. First and foremost, CINV, it's a substantial and growing market. There are over 5 million moderate to highly emetogenic chemotherapy cycles that require treatment annually. What's nice about our portfolio, SUSTOL and CINVANTI, they're established, differentiated CINV products that are complementary to each other. So when you think about how this disease state is treated, you've got most of the time, it's a 5-HT3 and NK1. There are three or four drug regimens that patients are getting. So a 5-HT3 and NK1, dexamethasone, olanzapine is also used in that treatment.
From a commercial perspective, CINVANTI continues to have a 27% share in the market despite fosaprepitant and generic entering the market four years ago. So in September 2019, it entered the market. At that point in time, we had a 40% share. We saw a drop-off the following year. But over the last, really, four years, we've consistently maintained a share of 27%. The sales performance is really driven by a focused commercial strategy and execution. We have a small team, a small footprint where we have four national account diRechters that are highly focused on the clinic segment. And then we have eight national account diRechters on the hospital side, which spend about 25% of their time on CINVANTI. The portfolio has generated over $630 million since inception, with our first commercial launch happening in the fourth quarter of 2016 with SUSTOL.
In 2023, we exited at $107.9 million for the portfolio. It's a highly profitable franchise, as I mentioned, small commercial footprint. Then we have a robust IP estate with patent protection through 2035 for CINVANTI. So this slide is a little bit of an eye chart. But I think there's some really key areas that I wanted to point out for you. So CINVANTI is an NK1. It is polysorbate 80-free. And it's approved for both acute and delayed CINV due to both HEC and MEC. And I had mentioned earlier that market has 5 million annual cycles. We launched in January of 2018. Shortly after our launch in September of 2019, Fosaprepitant went generic. Some of the key differentiators with CINVANTI, first and foremost, it's free of synthetic surfactant, polysorbate 80.
Polysorbate 80, which is an Emend, has been associated with infusion site reactions and hypersensitivity. That is a big differentiator for us in the market. Secondly is the operational efficiency of the product. So CINVANTI can either be given through an IV infusion or can be given via a two-minute IV push. That two-minute IV push is a big advantage for us. So the next slide here, I want to talk a little bit about the market and so how we frame the market. So there are four products that we define as part of our market basket, one being CINVANTI. These are all IV NK1 products. One is Fosaprepitant. The other is IV Emend, which was a brand prior to Fosaprepitant going generic. And then IV AKYNZEO.
IV AKYNZEO is a combination product of a 5-HT3 and NK1 that we consider part of that market basket. What is really interesting about this space is the absolute growth that we've seen in the NK1 space. 2017, which I probably should have up here, but 2017 was about 1.4 million units. We continue to see growth. If you look between 2018 and 2023, there was over 56% growth in the NK market. Then the recent three years was over 30%. If you look at this, almost every other year, there's double-digit growth within the market. It continues to grow. One key thing I want to point out here, right? CINVANTI is an aprepitant. APONVIE is an aprepitant. So it is the same compound.
What's really interesting about this market, if you think about the growth that we're seeing in the NK1 market for CINV, what could that mean for the APONVIE market moving forward? All right. So I want to touch a little bit on performance. So we mentioned consistency, consistency, predictability of the brands. If you look at the last five quarters, we grew 4% versus the same time last year, so Q1 2024 versus Q1 2023. So we grew 4% in units. But our share, if you look at each quarter, has hovered between 27%-28%. If I expanded that even further back in time to late 2020, that's around the kind of where we've been maintaining our share. The 170,000 units that we exited Q1 at is our highest unit number since before the generic entered the market in September of 2019.
We look at our business also by two key segments. One, we look at the hospital segment. Two, we look at the clinic segment. The clinic segment, we defined it really as those Physician-owned practices or community oncology. And so the hospital segment drove 112,000 units in the first quarter. Predominantly, about 80% of that was driven by the 340B market. And then if you look at the clinic segment, kind of flat year-over-year, you see a little bit of fluctuation up and down based on buying patterns of clinics. But we exited the first quarter at 58,000 units and a 28% share within the clinic. So we really have consistent performance across segments and across the quarters. This slide I'm going to spend a little bit of time on. And this is one I think is truly powerful.
The reason being is there are about 30 NCCN hospitals across the United States. This is a kind of very prestigious designation for these cancer centers. If you look at the cancer centers up here on the list, at the top, we've got Memorial Sloan Kettering. They have a 99% share of CINVANTI. They've been on board with us since early 2018 when we launched the product. You've got other large cancer centers such as Duke. You also have Dana-Farber on the list and a number of others that I can mention. These are just the NCCN institutions. Outside of that, from coast to coast, we've got UPMC that is a large user of CINVANTI with an 80+% share. University of California continues to grow quarter-over-quarter. There are a number of significant key IDNs across the United States that are using this product.
But really, one, we're an NCCN Category 1 product. And then also what really speaks to the IV push of the product, the operational efficiencies of the product, is ASHP, the American Society of Health-System Pharmacists, recommends switching from an IV infusion to an IV push whenever possible. And they define that even more of anything that's under 5 minutes of a push time. And so this, again, as a reminder, CINVANTI is a 2-minute IV push. So last slides, I'm going to touch a little bit on SUSTOL. So SUSTOL is a 5-HT3. The 5-HT3, it's the only subcutaneous 5-HT3 able to control and sustain therapeutic levels of granisetron greater than or equal to 5 days. What's nice about this is it also uses the proprietary Biochronomer technology similar to ZYNRELEF.
That's how we're able to maintain those therapeutic levels of granisetron over a 5-day period of time. The drug launched in October 2016. Almost immediately after March 2018, we had palonosetron, Aloxi one generic for palonosetron. So we have been very comfortable competing in generic markets within the oncology space. One thing that you'll see on here is the patent expires in September 2024. However, the beauty of this proprietary Biochronomer technology is we believe there is a very high bar for entry. And so we do not expect any competition within this space. And lastly, the market. The market is mostly made up of 5-HT3s of generics. So 98% of the volume is made up of generics or generic-level priced products. When we define this market, we're defining it really with four IV products.
One is Aloxi, which was the brand before it went generic, palonosetron, which is the generic form. You've got SUSTOL and then IV AKYNZEO again, which is the combination product. Again, you're looking at a market that grew from 2.4 million in 2018 to over 3 million in 2023 and with 9.4% growth year-over-year. We did 33,000 units in 2023. We exited the first quarter at 10,000 units. Continue to move along and grow this business. I think I'll leave you with a couple of things. Our products continue to have a differentiated value in the market. CINVANTI, with the PS80 formulation, being key to our success as well as the two-minute IV push, which gives the operational efficiency and really cost savings to hospitals. These markets continue to grow year-over-year.
Chemotherapy continues to be the backbone of oncology care, which there is a need for supportive care. So with that, I'm going to close and transition to our Q&A.
Are there any questions?
Hi. Thanks. Tim Chiang from Capital One. Very informative morning session. Craig, you highlighted with ZYNRELEF the prefilled syringe being sort of the Holy Grail for the product. What has to get done over the next 12 months such that you can get that product across the finish line? You're talking about the VAN? VAN and the prefilled syringe. And the prefilled syringe?
Yeah. So right now with the VAN, we're putting the finishing touches on the submission. So all the testing is done. And the reports were finished up just recently. And just to give you kind of depth and breadth, there were like 100 different reports that needed to be written up or needed to be edited in order to pull together the CTD, the common technical documents for this submission. So all of that work is in the finishing stages of it.
And so the VAN will go in within a few weeks, if not sooner. So that's imminent. The prefilled syringe, we continue to work on stability and sterility with that particular product. So I mean, I was mentioning earlier, some of the challenges with ZYNRELEF really are a function of what makes the compound great with the viscosity. Also makes it difficult to store and be stable. So when you do sterility on a prefilled syringe, part of the problem is that that sterility, the way that you do it, may bring moisture along with it.
When you bring moisture to ZYNRELEF, then you obviously need to figure out how to deal with that. So as I said before in my presentation, we're looking at the end of 2026 as our goal. Backing into that, we're really looking to try to have something that's up on stability sometime early next year is the hope, so.
Okay. Great. And just maybe one follow-up. I mean, it seems like to get the product, ZYNRELEF, to the surgeon, it's really the tech that has to basically prepare the product, right? So it's really getting to the techs at these ASCs. How can you sort of get to as many of those people and get them to sort of get trained?
Yeah. So the OR technicians that you're referring to, they're typically responsible for handling that sterile technique, the aseptic process, drawing it up, right? So we need the champion. We need the surgeon to want the product. But then anytime you introduce something new, we're humans. We don't like doing a new process. So you tell our OR Surgical Tech, "Hey, you need to do this for two minutes." That changes their whole day, right? But the key with that is the feedback loop, understanding what that two minutes did for that patient. So educating, "Hey, you're going to reduce opioids, reduce pain. They're going to have a better functional recovery, better long-term quality of life." They start to see that information, hear what's happening for the patients. That two minutes doesn't become as burdensome.
Yeah. If I can add to that, again, I'll give you kind of a very layman's view. I hadn't been in an OR surgery ever until I came to this company. The first one I went into, and I watched the transition of the nurse holding this with their fingers while the other one drew and turning this thing up. I just kind of watched this complexity of it.
It didn't take you long to figure out, "Okay. This is a little bit of a problem." Once you got to the sterile field, it was kind of game over. That's why we keep saying with the prefilled syringe, "Look, this would be game-changing because it sort of does away with all that." Then you can talk more about the drug and less about the device. But again, the things that we like about the VAN, I think what Bill showed in those slides, it was really telling is that when you have the VAN, you drop that in. Once you snap on, you're sterile.
And it just makes things. It just takes that transition, so it makes it so much easier. But the other point that I think Thomas was pointing at is that they're living and breathing in these places every day. And so now you've got an advocate in there sort of helping with this process, getting it pulled from pharmacy, talking them through it. We don't have those type of relationships. And so when it comes from these guys who are seeing them every day and knows them by first name and all this, it's just different. So yeah. Please.
Yeah. So let me add something to that real quick. I will just tell you, for Orthopedic Device Reps and for people who don't know, trying to get a scrub tech to put together an external tibial alignment guide for the first time is much more complicated than getting them to do this. And what I would say is that a lot of times, maybe even the circulator, depending on the technique, could be putting it together and having it ready to go.
So this is about having people. It's about education, number one. But it's about having people on the street inside the clinic or inside the hospital or inside the ASC who can show them that. And so the whole point of building out a network and putting people. These are people that are there every day. They're there anyway. They're there for the cases already. That's the key.
Yeah. One kind of quick funny story. When Thomas and I first met, I go down to Atlanta, and we showed him the different devices. And we showed him the VVS. And he was like, "Look, I love the drug." He's like, "That's a little tougher, this and that." But when we showed him the VAN, he's like, "Hey, this is going to really solve this." And he goes, "I can't wait till this comes out," and so forth. So again, we know we're onto something. We know this is going to improve it. But again, I think this relationship is going to be really key in that.
Okay. Great. Thanks.
Thanks. Go ahead, Carl.
Yeah. This is just to clarify. I think you mentioned 50,000 per orthopod with respect to ZYNRELEF. To the bottom line, is that revenue, or is that to the bottom line? Just for clarification. Then I have a follow-up.
Net revenue.
Net revenue. Yeah. Okay. Good. Good. Thanks. And then given clearly, you're going to focus on your 4 FDA-approved therapeutics. But you're building this infrastructure and distribution. And obviously, you're getting a lot of mindshare and penetration here. What opportunities do you see for other product acquisitions to lever that as you build it? Thanks.
Yeah. So actually, there's two things there. So one of the things that we really hadn't talked about a lot, I think what I came out of a company that was in transplant. And in the 6 years that I was there, we were very successful. And I never went to 1 surgery, not 1. And our Reps weren't in those surgeries. The issue we have is that our Reps are living in these surgeries. And so they can't go to other places in the hospital.
So again, part of this partnership is not only allowing our Reps to sell to the Physician but getting them out of that OR where they can spend time in other parts of the hospital and some of these other surgeries. So to your point, what we're looking to do as we move forward from an M&A standpoint and again, we're going to get fairly active here once we got the expenses in line and so forth. But we know we have a lot of opportunity on the oncology side. We have a team that has deep relationships. We can certainly utilize that. I think on the acute side, again, with development capabilities, I think that'll be sort of the next phase.
And the creative deal behind that, we'd like to get in development, maybe a late phase II, phase III, or something like that that would fit with what we're promoting. So that's kind of how we're sort of visualizing this and how we think we'll move forward strategically.
Yeah. Hey, Brandon Folkes. So when the VAN comes online, can you just help us think about what that does to the uptake curve and where the opportunity lies? Is that in going to new accounts who previously may have not used ZYNRELEF? Does that convert current users and just sort of go deeper in their surgery? And then can you just elaborate a little bit? Do you have to go back to P&T committees and just kind of the work to be done till we see that uptake curve bend?
So we wouldn't necessarily have to go back to P&T committees, right? Because the drug, ZYNRELEF, is approved. We just obviously are making an enhancement to the kit. I can tell you that one of the challenges is sometimes we lose customers because of sterility concerns. I think we could probably gain back overnight at least 10% of the customers that would come back based on now addressing that challenge in the OR. So I think that's a for sure instant. But the bigger thing that it does is it allows us to move on from an account quicker. Currently, due to traveling nurses and scrub techs or just if a hospital has 80 ORs, that could be 80 scrub techs that you have to train, probably 120. The VAN, once you do it one time, you'll never forget how to do it.
Or it's almost intuitive that somebody could figure out how to do it on their own without needing to be trained. So it significantly improves our ability to go deeper and wider within accounts.
Well, thanks for hosting us this morning and bringing the entire team. It's great to meet everybody. You highlighted the ZYNRELEF strategy, really focused on the ortho procedures, especially now with the CrossLink partnership. How do you view the rest of the opportunity outside of ortho and soft tissues just in terms of the overall procedures and whether it's something you can target with your sales force or it would require another CrossLink-type partnership to do?
I'll hand it to you. Just go ahead.
All right. Yeah. Just on that opportunity, soft tissue is definitely significant. When you start to look at the evolution as you get into an institution, we target ortho because that has some of the highest pain associated with it and the most impact, right? Once you're through the doors, the other Surgeons start to become aware of it. Then we adapt to those soft tissues. So seeing it go, start hips, knees, go into trauma. Then pretty soon, you're doing abdominoplasties, breast augmentation, C-section, things that have a significant degree of pain where you'd typically use opioids. That's where ZYNRELEF is going to be used to minimize or reduce or eliminate those opioids. So a lot of these soft tissues procedures like hernia, for example, we did a study. 95% of patients were opioid-free. In America, we prescribe opioids for hernia surgeries in 70% of patients.
So changing that paradigm and making what is expected for the recovery of these patients, for the surgeons, putting in that new standard of care, it's going to be a huge opportunity for us. So definitely, there's a focus there. And we'll progress that way.
Yeah. Again, sir, I would just add that the surgery that you saw in the video, you saw 5 or 10 minutes of him closing and using our product. There's two hours before that that our rep is standing there. That's our issue, right? And the other issue is that, again, as we're growing accounts quickly, we also continue to lose accounts from time to time, as David mentioned. So VAN, prefilled syringe, having people in the surgeries is really going to help not only help with the growth but also close the loop as far as accounts that we've lost in the past, so.
Yeah. You went. Can I add one thing to that? I'll add one thing to that is, as I mentioned earlier, if you're a pharmaceutical rep and you're out knocking on the door, and maybe you got one surgeon you're trying to get into. But if you all of a sudden have access to a facility that you're going in because the medical device rep that you're partnered with lives in that facility every single day and is there every single day, and now you have the ability to piggyback into that facility with that Medical Device Rep, and maybe you're there to see how the cases are going with Dr. Jones, but next thing you know, you're going to be there all day and meet five other surgeons, you start to change the game. So it's a real big opportunity.
Yeah. I'll just add, as we were talking about strategically, sort of this enter and expand opportunity, one of the things that we talked about when we joined last year was our representatives were chasing every potential opportunity within our label. And so I mentioned it's sort of a blessing and a curse strategically or from an execution standpoint. It further emphasized our bandwidth issue.
We would have some Reps having success in plastics, some Reps doing ortho, some Reps doing this. It really allowed us to sort of characterize, "Let's prioritize one area where we know we're going to do really, really well, and then we'll build from there." So as the quarters go on and we see this CrossLink partnership take shape, as 2024 goes on, we talk about it being the year of Ortho. We'll start to expand from there again as our bandwidth in the field sort of gets them out of the OR. Now we can start talking to other surgical lines. So that's how you're going to see us start to articulate our growth.
Good morning. Les from Truist Securities. Craig, maybe this one's for you. It appears ZYNRELEF is covered under NOPAIN Act. So the NOPAIN Act should be incremental to you. What are your thoughts on the competition from Exparel, gaining from the reimbursement? And then second for Dr. Robbins, any thoughts on secondary agents for pain management post-op, specifically VX-548? Thank you.
And in regards to the NOPAIN Act, yeah, it kind of levels the playing field, as you're alluding to, when that goes into effect because ZYNRELEF is currently reimbursed in the HOPD and the ASC. And then the other products like liposomal is not reimbursed in the HOPD. When NOPAIN Act comes into effect, Exparel will also be reimbursed then in the HOPD setting and the ASC just like ZYNRELEF. So it becomes a clinical conversation, right?
So when we evaluate these products at a P&T, we're going to look at the overall clinical impacts. And ZYNRELEF , as we showed, has the superior clinical outcomes, opioid reduction against bupivacaine and pain reduction, where Exparel did not have those similar effects in their studies. So when you evaluate it clinically, NOPAIN Act is going to be a benefit by creating awareness, by re-engaging these P&Ts again, these hospitals. They're going to start to look at, "Which product are you going to have on formulary? Why are you going to have it? If not, what aren't you doing right for your patients," right? So it's going to stimulate the conversation again about long-acting analgesics and bringing that to the table, so a benefit overall. What was the second question?
So for post-op pain management, essentially, what other agents in the clinic? Vertex had recently positive phase II data. What are your thoughts on that, and how will that kind of enable you with more agents to contribute?
Sure. I'll tell you, I'm mildly familiar with the Vertex product. And I think that there is a position for that. But I think it's going to be we talked about this a little bit last night. I think there's a lot of opportunity for synergy there. It is an oral version, though. So it's going to have its own challenges with loading and everything. But I think that there is a lot of potential for hitting different receptors.
The thing about anaesthesia from a pain standpoint, we have always tried to get as close as we can to the incision. But we can only get so close. That's the biggest difference for us with this drug. It's not an anaesthesia drug, but we can't because we can't get as close as they can. I tell surgeons when I talk about this drug now, it's really see pain, place drug. So wherever you're hurting the patient, drop the drug right there and make a difference. And I think that when you add in another drug that comes out with something like that on top of that in the post-operative period, just like you see with the multimodal approach post-operatively, I think it only adds a synergistic piece to that. I don't see it really as a competitor more than as a synergistic opportunity for both products.
I think the other thing that we didn't really talk about either is I think when you look at these two drugs, you've got one that treats pain, one that treats nausea. And the difference in subjectivity between those two is really huge. When you look at a drug that's treating pain, the subjectivity of pain in the perioperative period is huge because no two patients will experience the same insult the same way. But when you look at a drug like APONVIE, when you're looking at, "Can I stop a patient from vomiting or not?" we all know if a patient vomits or not. And I think that's going to show a level of success with APONVIE that's going to be able to piggyback off of everything with this company.
I think that it's going to—I mean, I think that drug is so good that clinically, it's going to prove itself over and over and over again when we don't have people throwing up because people are always going to hurt to some degree because it's surgery. And I think that's managing expectations. But if we can stop patients from throwing up, it gives us a credibility from a corporate standpoint that's unmatched, I think, so.
Other questions? Please.
This is Clara from Jefferies. Thank you for a very informative presentation. So just trying to understand a little bit more from the perspective of ZYNRELEF's reimbursement. So, just wondering under what kind of circumstances ZYNRELEF is considered as part of the surgical bundle and when it's not and it's reimbursed separately. And after the NOPAIN Act takes effect beginning 2025, does it really fundamentally change how ZYNRELEF is reimbursed? And also, maybe just clarify whether the launch of VAN and prefilled syringe changed anything about reimbursement?
Yeah. Great questions. Reimbursement is a mystery to many. I think they make it as confusing as possible in the healthcare setting. So the standard model is the DRG model. You get paid a bundled price for X surgery, $10,000 for your total knee. That's what you get typically. It doesn't matter how long you stay, what medications you use, how many of those medications you use. You get your $10,000. When ZYNRELEF was approved, we were granted pass-through status.
So that allowed us to bill for it separately. So you get your DRG. And then the hospital outpatient procedure department, we say HOPD all the time, they're able to bill separately. So they get their $10,000, but then they also get reimbursed for the ZYNRELEF. Same thing happens in the ASC, the Ambulatory Surgical Center, where they're going to be reimbursed for the surgery and reimbursed for the drug separately. So when NOPAIN goes into effect, nothing's changing for ZYNRELEF from that perspective. That's why we say it won't impact the facilities. But the NOPAIN Act is going to give the facilities the confidence that they're going to continue to be reimbursed because our pass-through status will expire Q1 of 2025. And that's when NOPAIN goes into effect.
Facilities also look at NOPAIN as a positive for the fact that it's set to go through 2027 and likely beyond that. So they're going to know this reimbursement is going to continue. And it's going to re-stimulate these conversations around the product and what we're providing for patients in that setting of care.
That's also within it, with knowing that even though the NDC will change with the VAN. The NDC will change with the VAN and also the prefilled syringe. They'll still link to the same reimbursement code. So it won't change that at all.
Got it. Thank you.
Other questions? Okay. I'm going to make just a couple of closing comments. I'm trying to tie in a few things I wrote a couple of notes down. So bear with me. Yeah. So just I want to tie a few things again.
I love when I leave a room, and I'm sure I just touch on a few things that I think were mentioned today that are really, really important. One, I hope all of you guys know that we've got our hands around this business now from a financial standpoint. We're managing this. We're going to continue to manage it. And rest assured that we'll go on as we move forward. I did want to mention we talked about APONVIE, okay? We put some numbers up there that I just want to make sure everyone understands. So David showed 305 accounts that we have now that we know are going to use the product or in the process of using it. And it really becomes now a time to conversion. And so at my last company, we had a transplant drug.
Once we got an account and got protocol, it was an annuity situation. APONVIE is exactly like that. So the takeaway we were trying to show you guys is that these 305 accounts, if we all go home today and go to sleep, okay, as these things come on board, if they just do the minimum of what we think of 20%, it's a $15 million run rate, period. So again, we're not doing that now. If you think where we're at sales for APONVIE, we haven't had a $1 million quarter yet. But we know in the bag, there's $15 million that will be coming in at some point. And so I just think it's really important to note that if that wasn't clear. And then again, then there's the market potential on top of that.
So as we convert accounts, I think as you'll see when we move forward, we'll start to show this as a metric, like how many accounts we have and kind of the value of those accounts and how we're perceiving that on a tiered basis. So I just wanted to clarify that. Again, Bill mentioned VAN and the timeline there. The really last thing I would say is that I think one of the things that you heard consistently today was tailwinds, NOPAIN Act, GLP-1s coming into play, and how that affects APONVIE. All these things were really pointing with our product line specifically are kind of moving this thing.
The last thing I would say is that when you looked at some of the market shares with CINVANTI and really major, major accounts, one of the things that they love about this drug is the consistency of it, the IV push. I think we can make a bit of a correlation to APONVIE in some of these centers and how we're seeing the reaction. The beauty of APONVIE, the last thing I'll say about it, is that when we gain an account, we don't lose them. I mean, we keep them. It's always a positive experience. And as you guys have seen with ZYNRELEF and some of the prep, we've had some nuance to that product. And again, it's going to continue to improve with VAN, our CrossLink partnership, and then ultimately the prefilled syringe. But I think those are key takeaways.
Just lastly, I wanted to say I think this has been a phenomenal day. I'm glad we got to meet people in person finally. I know a lot of you, we've seen each other through Zoom and things like that. But for us, this was very helpful. And we can't thank you guys enough for coming out and giving us the time to tell you our story. And to our experts, I said this when I started the meeting. I've seen these guys in a room, and I leave literally feeling so much more confident about what we're doing and the clinical value of these products. And I think you guys today got to see a little bit of that and what this is really like in real practice and how this is really helping these patients. So with that, I just want to thank everyone. Again, we'll try to do more of this in the future.