All right, perfect. Good afternoon, everyone. It's afternoon. Hopefully, folks were able to grab some lunch. I had a nice blueberry muffin for my lunch, so hopefully your lunch is better. But thanks for joining us at the William Blair Growth Stock Conference. My name is Margaret Kaczor Andrew. I'm the research analyst here at William Blair that covers Glaukos. Before we begin, I'm required to inform you that you can obtain a complete list of research disclosures or potential conflicts of interest at williamblair.com. With that, very pleased to introduce Alex Thurman, CFO of Glaukos, with us. We also are pleased to have Tom Burns as well, who's sitting in the audience, listening, as well as Joe Gilliam, the COO. So appreciate it, guys.
Great. Thank you, Margaret. I have not had lunch yet, so I'll look forward to that. But thank you all for coming this afternoon, and thanks to William Blair for hosting us today. That we can talk a little bit about Glaukos, and we're glad you're here. So I'll let you all read this. No, I'm just kidding. All the legalese we'll skip, and we'll start with kind of a snapshot of—I think back, I'd like to share the journey of Glaukos. When Glaukos started over 20 years ago, it came to be because of an idea: How can we treat glaucoma patients better? Can we do something that will alleviate the patient from a lifelong burden of topical drops?
As that journey started and the ideas were flowing, the iStent was the first thing that came to be, and it was a long and hard journey to get there. Those of you who have remembered the story, you know, it was difficult to get that iStent passed through the FDA, and when we did, it was limited to a combo cataract site of service. But the ambitions of the company were much more than that. The idea around the company was: How can we really change the mindset, change the philosophy of physicians to get to this more interventional glaucoma mindset and really help these patients?
So you see there on the slide that, you know, over 15 years, we've been working on something called iDose, and everybody, most everybody's heard of that, but it's been a long time coming, and we're excited to finally be there. Over that course of time, there's been over $600 million that we've reinvested in the business in R&D. Not just on iDose for sure, but between the iStent, iStent inject, iStent infinite, iDose, and other things that we're working on that are in the pipeline, we've invested a lot, and we continue to invest. The iDose trial, 1,150 subjects. So it was a large, pivotal trial that took into account, you know, the largest one that we had ever done, just to show that the iDose product was safe and effective.
We had to build a new manufacturing facility, and, interestingly, we went out to a lot of contract manufacturers to see if they would be willing to manufacture the iDose, and of all the bids we got, there were none. We got 0 bids. No one wanted to touch it because it was just so small and so difficult to manufacture, and so we had to do that ourselves. And so we ended up building a state-of-the-art manufacturing facility down in San Clemente, California, and, here we go, and, and we're on our way, doing it ourselves. And last but not least, we went ahead and had to submit our NDA, but it was also under this new regime where it had to be covered by both the drug and the device side of the FDA.
So the application turned out to be over 100,000 pages that our team had to put together that got reviewed, and I'm sure those government bureaucrats loved doing that. So what happened? We were blessed with an approval. So iDose was approved back in December, and it was launched just this past February in a controlled way, and it, our pioneering journey around interventional glaucoma is just beginning. I think everybody knows what iDose is, but for those of you that don't, it is this very micro-invasive drug delivery platform that is injected into the eye in a simple procedure that will and is designed to provide therapy to the patient for up to three years. You can see on the chart it's very small, you know, 0.5 millimeter by 1.8 millimeters.
And you can imagine that the magic of this is the canister is in the formulation of the drug. So we took a prostaglandin, travoprost, and we had to formulate it in such a way that not only would it fit into this canister but also be able to elute over time to give the therapeutic efficacy that was needed to the patient over a certain amount of time. We were hoping to get at least a year, but the trials were able to show us that we were able to get, for most patients, up to three years of duration with this product. The other key component to the design of the iDose is on the right-hand side, where we designed it to be a fixed anchor-based system.
So this device goes into the eye and is anchored in the scleral wall, and that provides a lot of safety features and allows the, you know, a non-floating device to elute the drug over time. Then you ask, why? Why did we need iDose? Don't we all? You know, the current standard of care is topical drops, and they've been around for 40 or 50 years. Don't they work? The answer is they do, but only when patients use them. There's been many studies out there that have shown that patients just don't take their drops. But why do they not take their drops? Well, there's various reasons. The first is, you can think of very simply, older population, and a lot of those older folks, it's very difficult. They have kind of tremors or shakiness. It's hard to put those drops in.
But for even a greater percentage, there's other side effects that come along with those topical drugs. There's dry eye disease, there's red eyes, there's other ocular surface diseases that happen. You can see on those pictures. And so patients just, they decide, "You know what? It's not worth it to me. I don't like it. I don't feel any pain. I don't see my vision degrading. I'm just not going to take these, these drops anymore." And as a result, their pressures continue to stay high, and the glaucoma progresses. And so iDose was a way to get around this and was designed to, to overcome this, this phenomena of non-compliance with drops. There you go. Very nicely done. I see the man in the audience taking a drop right now. The data from the phase III trials shows that this works.
If you can get the drop in, or the drug in, I should say, behind the iron curtain of the cornea, it's super effective. So on the left-hand side, you can see the, you know, there was two arms to the pivotal trial, and you can see what the IOP lowering rates were. Compared in the gray was another prostaglandin called timolol. And on the right-hand side was a very interesting data set where you took on the left-hand bar, this was the pressures inside the these patients were about 18 millimeters of mercury under using drops, using topical drops, and then they were washed out, and they were measured again. And so without any prostaglandin drops, they were sitting at almost 24 on their pressures. And then an iDose was implanted in these patients, and it was measured at three months.
You can see that the iDose actually reduced over 1.3 milliliters more of a pressure drop than just having the drops alone when they're used. So the iDose was shown to be super effective and very efficacious along with the safety profile. Another benefit that we saw coming out of the trial was that over 81% of patients were completely medication-free after 12 months. And so, as these patients progressed through the trial, they were found that the iDose was doing what it was supposed to be doing. It was lowering their pressures. There was no need for additional medications to be dropped on top. And so that was a great outcome.
Below, you'll see in the phase III trial, at 12 months, 93% were still responding to iDose at 12 months, and then the lower row shows on the phase IIb trial at 12, 24, and 36 months. So you get out 3 years, and you can see that almost 70% of patients are still responding, having their pressures well controlled after 3 years. This is an interesting piece of data that we like to show. One of the things that we did was we went ahead and were measuring the amount of drug inside the eye at every 3 months, let's call it, right? Over a period of 2 years.
And so that top graph shows you the amount of drug that was being still in the eye by taking an aqueous tap and measuring it, which was you know, important because it showed that there were still therapeutically relevant levels of drug in the eye at all those time periods along those 3 months for over 2 years. And the bottom graph was shown is designed to show you that we took out the iDose canister, and we measured how much juice was still left in it, and it was came out exactly as we thought.
So again, you show that the elution rate is happening at a very constant rate over time, and when you get to the end of the two years, there's still 16% of the juice still left in the canister that can be eluted over the next time period. Safety. Safety was a very important consideration for the iDose trial, and as you can see here, we had great safety outcomes. Again, it goes to the fact that I earlier alluded to, which was the fixed anchor system. The big, the biggest safety concern was always ECL, and we really had no significantly statistical evidence of any ECL loss in the iDose study.
But in addition to that, there's some other safety signals that you can see on the screen, but just a really stellar safety profile to the product. This just shows you the whole platform as far as the treatment paradigm going from ocular hypertension all the way out to refractory glaucoma, and that the Glaukos portfolio can handle all of this. So you have iDose TR that has a wide-open label and can treat any patient from the beginning to the worst case of glaucoma. You have iStent infinite that's been approved for refractory or advanced patients, and then you have our legacy iStent inject that handles everything in the combo cataract arena.
So, as we go through the history, when we started with iStent and, iStent, the original iStent, we had, again, as I mentioned earlier, it was, prescribed to do within the combo cataract. That market was about 500,000 eyes. The next level that happened was iStent infinite, which is indicated for more advanced and refractory eyes, about 200,000 eyes. But when we get to iDose, it's a huge market opportunity for us, estimated at over 1,000,000 eyes. And because the label is so broad and wide open, we can handle that, and, the product can be used interventionally as opposed to reactively. We're launching the product in a very controlled manner, which is what we've done with all of our products.
This is just a timeline of all the kind of the milestones that we go along. I'll just mention a couple of them. The first was, you know, again, the development, the manufacturing, and the ultimate approval by the FDA of our manufacturing facility that I mentioned. The fact that we were historically a device company that was aspiring to be a drug company that built this nano-manufacturing facility from the ground up, and then had FDA come in and inspect it, and to have zero 483B findings, you know, was, we thought, really remarkable and a testament to our operations, our quality teams, to be able to get that done, to be quite honest. And we're quite proud of that.
We also launch, are launching in the midst of launching the product in a very controlled manner. We're gonna start out very, very slowly because with a drug, it's different than a device. We're covered under a drug code, which we start out as a miscellaneous C code. A lot of our customers, you know, it's a miscellaneous C code is a little bit new to them, or it's difficult. It takes a long time to get paid. There's a lot of work involved, so there's no need to rush into the launch. The more important part is to start to launch with our trusted customers and learn from them as they learn from us. And then we also are taking upon ourselves a big effort to train their back office.
We have formed and hired a reimbursement group that goes into every office and trains their staff, their billing staff, on how these drugs work, how you are able to code them, and so that you have the best opportunity for success in getting paid on a timely basis and on a complete basis. The last thing is on that same theme. You know, we're starting out under this period of a miscellaneous C code, but the key to unlocking this is to get a J code, which we were able to successfully gain, and that will be effective on July first. You can see the number up there. The J code then allows a streamlining of Medicare payments, and that'll be even more streamlined once we get to October, which is when you'll have a J code plus an ASP.
But that was a key milestone to get the J code not only established but then ready to go as we enter into the latter half of the year. From a commercial perspective, the very nice thing about this as well is that we don't have to hire a new sales force. iDose can just drop into our existing bags of our reps that are out there, that are already trained, already have the relationships with these same customers. And so there's not a lot of investment required to launch the product from a commercial standpoint. Obviously, we'll have some marketing and some other spend that goes along with that, but as we launch, you know, we'll use our existing sales force, and we'll roll with that.
Again, as we get to the point where the J code is unlocked and our reps will be able to really run fulsomely in that period of time, that's when the product and the ultimate benefits and hopefully financial benefits will start to unlock, and we'll start to see that. I kind of mentioned this earlier, but the support system is a very important key part of the process as well. I mentioned the coding, the miscellaneous C code versus the J code, and so we've got this billing and coding support system, the reimbursement liaisons. It's now a required training that each office goes through and makes sure that they understand the differences on the billing. It's important that they understand the different patient populations.
You have not only Medicare fee-for-service, but you've got Medicare Advantage, you've got commercial, potentially paying patients. And so they need to understand the different dynamics with each of those and how to bill for those, how to code for those, how to prioritize those. We also have a group that we've formed within the last year or 18 months called Glaukos Patient Services, and this is around market access for the on the patient side. To make sure these patients understand what their insurance are, what their opportunities are, what their co-pays are, and helping them to navigate that process in the event that they need to. And the last thing I'll mention is on the bottom right. Glaukos is a company that's always been philanthropic in nature, and so we want to give back to the community.
We've had a program in place with our stents, where we are willing to donate those stents to countries or medical missions that are in need to serve those less fortunate populations. We're doing the same with iDose. So we've got. This is more of a marketed program where we're saying, iDose, your dose, and what we've committed to is making available any iDose that's commercially sold, we'll make available an equal number of iDose units for those same privileged or underprivileged populations, and we'll give those away for free. All this leads to kind of the wheel, the color wheel, we call it, which is the five platforms that we're developing within Glaukos. So you'll starting at the top, the iStent, that's been around for 10 years, which is the stent side of the platform.
Then we're now just launching iDose, which is the second platform. Again, I say platform because it's not just the travoprost iDose or iDose TR, but we're thinking about and working on what other drugs could we put into that same form factor and develop and use on patients. The next one in the purple is the iLink, which is also known as our keratoconus product currently, which is a drop. It's a drug that is dropped on the eyes of a patient that has keratoconus, which is a kind of a coning out of the cornea. To date, there's been no known cure for this. Many optometrists or ophthalmologists, when they see keratoconus patients, they try to deal with it with a hard contact lens and trying to hold that cornea in.
What the iLink procedure does is you put the drop on it, you shine a light on it, it bioactivates some things within the drug, and that strengthens the fibers around the cornea. We call it cross-linking, and that can arrest the progression of that disease right then and there and solve the issue. So we're continuing to develop future platforms, things around iLink. We are in our phase III pivotal trial, coming to the end of the next generation product for iLink, which is called Epioxa. We should have data released by the end of this year, and then an NDA submission, and hopefully approval at some point in 2025.
The big key difference here, and I'll just take a second to explain, is that our current iLink process requires what's called a debriding or a removal of part of the corneal epithelium, which is somewhat of a painful process, and it also makes recovery time much longer. Our new generation, Epioxa, will not require that same removal and allow much quicker time for not only recovery, but also the procedure time is cut greatly in half. So we're very excited about that opportunity, what that might mean. Most of these patients that have keratoconus are usually in their teens, so they're younger kids. It's tougher to get them away from school if they have a two-week recovery time, and so this should help greatly open up that marketplace a little more with the next generation Epioxa.
On the bottom is iLution, which is a super interesting platform because what we're doing there is it's a transdermal drug delivery system, where we're taking a cream, you'd see it in a tube in your bathroom, like a little cream, and we're putting drug inside of that cream. And the way you apply it is you just take a little dab, and you put it right on your eyelid. Boop, boom, and it absorbs and gets into your eye that way. When we first were approached with this, the CEO was very—Tom Burns, was very skeptical of this, you know, this technology, whether it would work or not. He actually allowed a couple of corneal specialists to take a look at it and try it, and they came right back to him and said, "This thing absolutely works.
You need to license it." And so we did. And so we're in the process of putting certain things in there. We've got, we've got it under study for dry eye, and we're currently in a clinical trial with travoprost, which is a prostaglandin for glaucoma. Which would then again change this whole idea if you've got a topical drop today that aren't being taken because of all the side effects, and you can deliver that same drug through a transdermal application, could be huge for those patients that are not wanting to undergo some sort of surgical procedure. Last but not least, in the kind of the orange color is the retina program. So very early, but, as our CEO likes to say, we have the temerity to try and become a retinal company.
What this is, is our, you know, the product that we have in development is a small bioerodible PGA, PLGA TKI type of implant that would be injected in the back of the eye and with a long-lasting delivery time. In our rabbit animal models, those retinal vessel leakage models were lasting up to two years with this implant, which is, you know, obviously a multiple of the products that are on the market today in duration. So we've just entered into a phase I clinical trial in the fourth quarter of last year, and we're progressing. We're going to watch it. It's obviously geared towards safety and monitoring that, but if this is successful, this could be huge.
It's a huge market, a $13 billion market opportunity for, for in retina for us. So that's kind of the platform look and what, what we're looking for and why we spend so much on R&D. We've just got a lot of stuff going on in the pipeline. Here's a bunch of, the milestone targets that we have in our pipeline for 2024. I'll just highlight a, a few that we haven't talked about. So the very first one is iStent infinite. I mentioned earlier that its, its current label and, approval is around refractory and advanced glaucoma patients, those who have failed on a, or failed previously on a topical drop or a medical or surgical therapy.
We'd like to expand that label to cover more of the mild to moderate population, so we're going through a trial to get that label expansion because we think iStent infinite is just a powerful product. iDose TREX, that is our next generation iDose. So, while we've just started on iDose TR, the iDose TREX is the next in the pipeline, and it's designed to last up to maybe twice as long as our original iDose. So what's interesting in engineering and geometry, for those of you who are into geometry, apparently you can take the existing same size canister that we have today, and by hollowing out a little bit of that canister wall, you can create almost twice the volume, and be able to load it up with twice the drug.
So our plans are to engage and start a phase III pivotal trial with iDose TREX by the end of the year, with hopes that we could get that approval by 2028. And then the last thing I'll say is, well, we've talked about some of these other ones, is the iLink third generation. So we talked about Epioxa, which we're hoping to get into the NDA submitted by the end of the year, but we're continuing to improve and look at the next generation, what's beyond Epioxa and that thing, so that's our iLink third generation. This slide just shows, again, all of the things that are in the pipeline that are currently publicly disclosed, and it's a big list.
There are many things beyond this that we haven't publicly disclosed, but you can see kind of by color, the glaucoma or the iStent, the blue is the iDose products, the iLution, the iLink, and then the retina stuff. So a lot of things that are happening within the walls of Glaukos and in the bowels of the organization as the R&D program continues to rock. Just some snapshot around kind of our financial and operational footprint. So you can see that over the last 10 years, we've had net sales growth of a CAGR of 30%. And this year, we're, you know, our latest guidance is for net revenues to come in by the end of the year between $357 million and $365 million.
We've had a long history of strong gross margins, so the mid-80s, and we continue to think that as this progresses and as we get approval and launch more products on the drug side, those are high-margin products, and we can have some accretion in that margin, so it's only hopefully going to get better. And then in the bottom, in the middle, the mix of our revenues and where they come from has diversified over the last 10 years, where you know, we started, we were just a U.S. company, but then we've opened it up rapidly internationally, and then we added the corneal health or the iLink business a few years ago, so that now more than half of that comes from international and iLink. So...
I guess I'll say a little plug for myself. Again, on the balance sheet, we like to think we have a strong balance sheet. You know, we ended the quarter with $279 million in cash, so we have a good runway and, as we look at all of those pipeline products that are coming. So some major accomplishments. We've talked about most of this. You know, iDose was approved last year. We began the Interventional Glaucoma campaign, let's call it.
And it's amazing to look where we were a year ago when we just started and now where this, this concept of IG is, how much it's talked about at society meetings, how much the doctors are into it and talking about it and getting their arms and their minds around it, how much presence is on social media around it. So it's really gone a long way. And as we look through what we're doing this year, I think we've, again, focused on iStent infinite and its adoption, making sure that we have a stellar iDose launch, which I've talked about, and the reasons why we're doing such a controlled option. We want to make sure that the patient and our customers have the best outcomes, and then really continuing to drive interventional glaucoma as a message.
'Cause that's the long game here. It's not a one-year process. It'll take 5-10 years to change the mindset from our friends in ophthalmology, that when they first see a glaucoma patient, they prescribe a topical drop, and then when the patient comes back and it's not working, they do a second, and then they do a third, and then ultimately they say, "Okay, you've progressed long enough. The only thing we can do is put a hole in your eye and do a tube or a trab." We need to change that mindset, and it wasn't their fault, the doctor's fault. It was really that there weren't tools available for them and to do something else, and now there are, and now we just need to change that mindset.
So last but not least, we have this mantra that says, "We will go first." And you can see obviously in our history and what we've done so far, we've gone first. You know, we started with the iStent, we developed the MIGS market, we built it, then we went into iStent Infinite and that opportunity. We've gone to iDose, we've gone to corneal cross-linking, and we're looking to do more with iLution and those other things that we've described. And so we're excited at Glaukos about what this means, and it's this idea and this culture is permeated throughout the organization, and we're just feeling like we're at the beginning of a great run within the company and what we have to look forward to.
So, we again thank you for your support and participation today.