Glaukos Corporation (GKOS) Earnings Call Transcript & Summary

Okay. Good afternoon, everyone. Welcome to the final session of Tuesday here at the JPMorgan Healthcare Conference. My name is Allen Gong. I'm on the Medical Supplies and Devices team, and I'm very excited to be introducing the management team of Glaukos today. Starting with prepared remarks, we'll be Tom Burns, President and CEO; and then during the Q&A, we'll be joined by COO, Chris Calcaterra; and CFO, Joe Gilliam. I will be running the Q&A session to follow prepared remarks so if you have any questions at all, feel free to shoot them over to me through e-mail, through Bloomberg or through the online portal itself. With that, Tom, it's all you.

Okay. Thank you, Allen, and good afternoon. I'm delighted to be able to present on Glaukos Corporation today. We founded Glaukos to transform glaucoma therapy, but as you know, our aspirations have always been far higher. And today, we seek to transform vision through developing novel pharmaceutical and medical devices that can truly transform the standard of care in corneal disorders, glaucoma and retinal disease. Let's turn to Slide 3. Our mantra has always been, we'll go first in innovation and it's always been at the core of what we do as a company. We're in the business of creating new marketplaces. We've already done so, where we've created pioneer and currently lead the global MIGS marketplace. We're doing so by creating a bioactive pharmaceutical marketplace for the treatment of glaucoma. We're doing so by creating inner channel-sustained drug delivery systems for glaucoma using iDose. We're doing so by creating transdermal dropless therapy solutions using our iLution platform for the treatment of anterior segment disease. And as you'll see later on, we're doing so as well by creating small molecule biorotables for the treatment of retinal disease. Let's move to Slide 4. Our focus is on execution, and we've been able to move the Dow markers during 2021 despite some pretty heavy external challenges. We fortified our MIGS global position -- leadership position. We've gone ahead and fully transitioned and successfully transitioned the Avedro business into glaucoma, and now, are set up for some strong iLink growth drivers. We've been able to reverse some initially proposed draconian cuts from CMS for the facility and professional fee payments for implantation of iStent device with a spirited campaign. We crafted a favorable IP settlement with Ivantis Corporation, and we have just announced FDA approval of a new device called the iPrime. We've also advanced our near-term pipeline considerably. If you think about it, during the course of 2021, we were able to present favorable data on 3 major products, the iStent Infinite, the iDose and the Epioxa device. We also finished our Phase III pivotal trial for iDose. And in terms of new R&D platforms and programs, we continue to move forward, as you see in this presentation, with substantial forward progress and as well have enhanced our ability to establish an in-license additional products that will serve the business, while we are creating the depth and breadth of the organization that will serve us longer term. Let's move to Slide 5. We put ourselves in a uniquely attractive financial profile position which provides a solid foundation for future growth. Over the last 7 years, we've averaged compound average growth rate of 30%, and this is despite the imposition of COVID. We've moved our gross margins from the mid-70s to the mid-80s and have held. We've intentionally diversified the business and now have over 40% of our gross revenues coming from corneal and from international glaucoma, and we've been able to maintain a healthy balance sheet while funding a number of these organic programs. We move to Slide 6. We're talking about 2022 as the year of the catalyst, both from a commercial standpoint and from a regulatory standpoint. As we move beyond our core offering from combo cataract into standalone glaucoma therapy, we'll be moving into new products with potential approvals of iStent infinite and PreserFlo. We'll continue to generate strong, robust growth from international glaucoma and we'll continue to invest strongly as well on the iLink side of the plate. And again, we expect to be able to be in a position to launch new products such as with the recent FDA approval of the iPrime device. When we talk about our near-term pipeline in terms of regulatory catalysts, let's focus in on a couple of major ones during the course of this year. By the tail end of this year, we'll be submitting NDAs for our iDose TR device and for Epioxa. And during the course of 2022, we'll be releasing our iDose Phase III data, which will supplement the data that we'll talk about today on the 3-year data for the iDose IIb. I think it's what's extraordinary, and I'd then ask investors to take pause and to reflect on is how far forward we've moved our portfolio of pharmaceutical products. We just announced entry and commercial enrollment in our 2 Phase II clinical trials for the treatment of dry eye and presbyopia. We expect to go into a third clinical trial in iLink next-generation later this year, and we also expect to be submitting subsequent INDs and IDEs in the areas of glaucoma and other therapeutic areas. We've established a new headquarters in Aliso Viejo, California. We've just moved in, and we are establishing a really strong and robust manufacturing in San Clemente, California, where we expect to have kind of full throated capabilities on the device and the pharmaceutical side. Slide 7. Our strategy for long-term growth and value creation has been to establish powerful novel technology platforms that will yield and spawn a cascade of proprietary paradigm-changing products that we can then put into a highly efficient commercial platform. We're focused on significant clinical needs and big ideas. Slide 8. The major big idea I want to leave with you today is the fact really something we've been practicing since 2012 with the advent and commercial release of the iStent product, and that's to disrupt the legacy of topical eyedrop therapy. I've been doing this for 30 years, and I tell you, iDose has been -- or topical eye drops had been the elephant in the room. They work well, but they don't work so well when patients don't take them. And there are numerable studies, both retrospective and prospective, which show that there's an extraordinarily high rate of non-adherence to topical eyedrop therapy. And when patients don't take these medications, their anterior segment diseases progress. There's a variety of reasons why they miss these drops: complex dosing formulations, forgetfulness, installation challenges and impositions to quality of life. Even when they do get these eyedrops in their eye, they're subject to a host of local side effects: hyperemia, hyperchromia, periorbital fat atrophy and toxicity from preservatives. And as we know, when they place these products into the tear film, most of the product will go down the nose and patients will be subject to systemic absorption. So we think there's a better way and we think that we have meaningful alternatives that we'll develop, which will change the paradigms of treatment for patients across cornea, retina and glaucoma. Slide 9, the technology platforms that will look to bring us there consist of 5 technology platforms that are distinct and pharma dominated. These will allow us to advance treatments in the cascade products across the host of therapeutic areas, being glaucoma, retina and cornea. And when we think about catalysts in the year 2022 alone, we're expecting at least 6 programs that will reach key regulatory milestones. These platforms have already yielded. If you look at the bottom of the Slide 9, our disclosed numbers of programs from 4, when we first went public in 2015, to 16 today. And I can assure you that there are many more that are under the hood that we're working on. We've currently invest approximately 30% of revenues -- gross revenues that we pull in into R&D. That's $275 million that we've invested into R&D as a small company, and we've done so on a cash-neutral basis. Slide 10. When we look at these distinct features of our platforms, these are invariably pioneering first. We're maximizing our proven ability to build durable, innovation-driven markets. And they should produce and spawn high productivity with multiple products per platform, reducing not only the cost to bring these products to market, but also enhancing their success probability. And these, again, will be directed against large and underserved patient populations. Slide 11. You can see the spawn and the fruits of our labors, when you look at how many products we'll have available during the course of this next decade. As I said before, if we stopped innovating today, I believe we have products that would serve and create great growth opportunities all the way through the year 2030. And clearly, we don't plan on doing that. We plan on continuing to innovate. When we look at the TAM that we're currently participating in, which is about $2 billion, we expect to be participating in a TAM that will approach $60 billion by the end of this decade. Slide 12. We'll deliver this through our leverageable commercial platform. We've got boots on the ground in 17 marketplaces worldwide with over 260 commercial personnel. And our goal and challenge will take these products on the right, which are imminently approvable in the states and beyond, and be able to make them stocking stuffers to go into the bags of these representatives to increase their productivity in a highly scalable model. You can see now, when we look at the middle of the page here, where just -- since 2014 alone, we've gone from less than $1 million in aggregate sales per representative to about $3 million. Turning to Slide 13. iStent, I believe, is the predicator of success of how these platforms yield multiple products. With iStent, we've already had iStent, iStent inject, iStent inject W, iStent infinite. iStent infinite, we expect to have targeted approval by the first half of this year, end of the first half. And because the data had been so profoundly good with iStent infinite, we expect that product to become our iStent SA and be able to serve in an earlier intervention capacity as a standalone device for the treatment of glaucoma. We're in discussions with the FDA right now on principally creating an IV, which will allow us to do that. Slide 14. I think many were delighted and surprised by how early we were able to talk about the commercial approval of the iPrime device, a viscodelivery system. We believe that this device is a minimally invasive delivery system that further supports the needs of clinicians. And we think it complements our technology and further expands our broad portfolio of innovative ophthalmic solutions. I think it's important, on Slide 15, that we revisit how great the data has been with iStent infinite. I showed these data with you at the last JPMorgan event, but when we looked at patients who had failed on 3 medications -- sorry, failed on 2 prior surgeries that were on 3 mean medications pretreatment and we placed them on the iStent infinite device, 76% of those patients achieved mean pressure reductions of 20% or greater while reducing their medication burden. 50% of those patients achieved pressure reductions of 30% or greater. We think that this makes this product a phenomenal opportunity for later-stage glaucoma patients. But I think increasingly, it also bodes well when we have iStent infinite serve as a standalone product for earlier intervention in glaucoma when we seek those indications. Let's turn to Slide 16. This is the product we've talked about and been waiting for, kind of the big kahuna in the next stage of glaucoma therapy. iDose is designed to address the ubiquitous issues of patient noncompliance. We expect to file this product in our NDA by the end of this year, and we expect approval in 2023. We already have the iDose TREX, which contains twice the amount of complement of a prostaglandin analog in final form factor review, and we're working hard on creating a complementary device using a potent ROCK inhibitor. I think as we turn to Slide 17, I think this is extraordinarily important. You've seen me over the years talk about the fact that we needed to have 6 months of therapy in order to have a commercial device. We would seek a year. That would be our ideal. We're now looking at 3-year data in a responder analysis showing that 70% of the iDose TR patients were well controlled on iDose on the same or fewer topical medications, even though many of those patients started on 2 and 3 medications. The mean drops and pressures were 8.5 millimeters, substantially high, providing the sustained dropless therapy. And even when we look overall at patients, responders and nonresponders alike, we find that iDose TR performed similarly to timolol at 36 months in terms of IOP reductions with fewer topical medications versus timolol. Importantly, as we turn to Slide 18, the data on iDose is safety as well is extremely important. It's extremely well tolerated. We found no ocular hyperemia. We found no periorbital fat atrophy. We found no clinically significant corneal endothelial cell loss and only one instance of iris color change. And these are precipitous adverse events and side effects that happen with topical medications. We think the value proposition for iDose is exceedingly important, 1 installation versus 2,190 eye drops per eye over the course of this 3-year period. Turning to the iLink platform on Slide 19. This has been a phenomenal success as we've successfully transitioned the Avedro business into glaucoma, and this represents the platform in full from of growth in our corneal segment. We have made headway, significant headway commercially with Photrexa. We expect to file for Epioxa with an NDA by the end of this year, targeting approval in 2023. If we turn to Slide 20, it's important to realize and to reiterate, that already we've achieved the primary efficacy endpoint in the U.S. FDA pivotal study by showing a 1 diopter mean difference in K-MAX of treatment versus placebo-controlled. And even in these early intervention patients, patients were able to reduce their K-MAX by 0.2 diopters. And at the 6-month crossover, 98% of those patients that were on placebo control chose to have the Epioxa treatment, which we think is an extraordinary validation of the value proposition. Let's turn to Slide 21 on the iLution platform. What if we could device a cream that could use the eyelid as a depot mechanism and a gateway to the auto bond system of the lymphatic system to drive product into the anterior chamber without having to form and to plummet its way through the cornea to be able to achieve therapeutic effect? And this is the concept behind the iLution platform. We already have entered clinical trials with dry eye and with presbyopia, and we expect to put this platform through the full paces with a glaucoma candidate and with our latest acquisition of Avalapse Demodex blathritis candidates in order to create a full array of products that we believe will have meaningful difference and change and challenge to the conventional therapy of using eye drops. You can certainly see how easy it will be to be able to just swab a little bit of a cream on the top of your eyelid rather than using eye drop therapy. Moving on to Slide 22. We've also made tremendous ground gaining activity in retina, and we're targeting biodegradable small molecule implants that will have up to 6 to 12 months of efficacy that will entirely change the standard of care which currently now is dominated by conventional biologic injections, that now imposed tremendous treatment burdens on patients because they have to be used every month or 2 in the treatment of AMD, DME and RVO. So we're investing in 2 intravitreal candidates, a multikinase inhibitor and a triamcinolone steroid device, a multi-kinase inhibitor for the treatment of AMD, DME and RVO and triamcinolone for the treatment of DME. We turn to Slide 23. The data are extraordinary, and like I like to say, terribly exciting and terribly early, but if you think about it this is a persistent retinal vessel leakage model in rabbits which is highly translational to human clinical trials. And we're seeing now with the injection of 1 or 2 of our biorotable small molecule impacts efficacy, powerful efficacy out to 10-plus months. So we are terribly excited about this opportunity. We think we are the company that can create this marketplace and change the paradigm and standard of care in the treatment of retinal disease. As we turn to Slide 23, we have made profound commercial execution since the launch of iDose in 2012 and certainly since our IPO in 2015. We've created a global MIGS marketplace. We are creating a bioactivated pharmaceutical marketplace for the treatment of glaucoma, and we have established 30-plus compound average growth rate over the 7-year period. But as we turn to Slide 24, I think what's below the topsoil is even more important, where we have multiple commercial and regulatory channels which are going to occur in the year '22 and 2023, and again, 16 promising disclosed R&D programs to drive a decade of growth in our future. So as we turn to the final slide, we believe Glaukos is different. We're a change agent. And we're delivering disruptive dropless therapies to change the current treatment convention using topical eye drops and were designed to improve patient outcomes. We have 5 distinct platforms that are dominated by pharmaceuticals and designed to generate waves to these new expanding -- market-expanding products. And we are -- both have proven that we are the people that are change agents, and we are proving that we will pursue game-changing therapies for these large and underserved patient populations in the future. So with that, thank you very much for your attention, and I'll turn it over to Q&A.

Got it. Obviously, so much to go through. I feel like every year, you somehow bring in more and more interesting things in the pipeline for us to really talk about. But I think before we really get into that, we kind of got a -- I hate to do it, but we have to talk about it. COVID-19, right, with Delta, Omicron, all of these different challenges in the macro environment. What did you see relative to your expectations in fourth quarter? What are you seeing in 2022? And how should we really think about the trend of the recovery going through the balance of the year?

Great question. Joe, maybe I'll ask you to handle that.

Right, Allen. So first, as we thought about the set-up for the fourth quarter or exiting the year, we did try to factor in COVID-related headwinds. I think as we look back and saw how things translate over the course of the fourth quarter in 2020, we tried to apply similar thinking, obviously, adjusted for vaccination rates and the like to 2021, knowing that we were likely going to see some degree of headwinds. You're right. Obviously, we sit here today amidst the Omicron insurgence and resurgence of COVID broadly across the globe. And it really varies by geography, right? I mean you see there's a full span of reaction state by state and country by country from the extreme of a geography like Australia, where in response to spikes in COVID-19, they tend to shut down either full states or the entire country to a degree, both economically as well as from a procedure perspective, for periods of time until they feel like they've got it handled. And that really spans to countries more like United States where we see a more of a disruptive headwind. I think what we're seeing domestically is folks continue to try to stay as close to normal as possible, but you're going to see efficiency headwinds because impacts practices. Individuals within those practices get COVID and that can shut them down for a period of time. They have to restore back some of the, call it, operating protocols they had when COVID was more prevalent earlier in the year. So these things all play a role. It's not as if we're seeing type of dynamics that we saw back at the beginning of COVID in April and May of 2020, but they certainly continue to be out there. As we look forward, I think we've always tried to take a bit of a conservative view when it comes to what the reality of all this means. And certainly, we're balancing that as we look through Omicron here. But I think as people continue to get vaccinated, as people continue to develop natural immunity from variants such as Omicron, hopefully, we continue to step closer and closer to some degree of the end of all this and getting back to business as usual.

Got it. And then just kind of like piggybacking off of that, just to look at 2022, right? And I fully recognize that you guys haven't preannounced, you haven't provided guidance for 2022, but it feels like there really are a lot of moving parts heading into the new year, right? Like as you said, COVID, unfortunately, is around to stay for a little bit longer. We have some reimbursement disruption to your core iStent franchise. You've got iPrime approved kind of -- I would say it's probably earlier than what investors are thinking of, and you also have the infinite on the way. So when we kind of look at where consensus is at right now at, say, roughly $268 million, so down slightly from this year, is that -- like is down still directionally where you think investors should be even with catalysts like iPrime, like infinite, like hopefully, Santen coming into the portfolio?

Yes. I'll probably stop short of getting too specific with respect to the 2022 numbers, but I will validate that there's -- there are a variety of, I'll call them, crosswinds, right, as we enter into 2022. And when you put all that together, you can certainly make a variety of cases when you think about how all that will unfold for the year. To your point, obviously, COVID will be what it will be, and we'll continue to navigate through that on a global basis. From a competitive standpoint, we think about that within the U.S. in some markets, some of the shifts there with Alcon's acquisition of Ivantis and other competitors, both on a U.S. and global basis, and taking that into consideration. From the U.S. glaucoma standpoint, you've got the reimbursement dynamics around the professional fee and what that may mean for volumes and demand for trabecular bypass stents such as iStent or iStent inject here in the U.S. From a pricing standpoint, I think things, with the changes that were made by CMS, you should see more stability there, but I think you still have to be -- continue to be cognizant of the things I just mentioned, right, the professional fee dynamics and what that can mean to overall pricing and the competitive dynamics and what that can also mean. But going into it, the setup is certainly far better than it was when the original proposed rules came out. Offsetting all of that, as you think about it, is what you said, a series of hopefully of new product introductions that both can drive the top line individually, but also collectively and what that can mean as the part of the overall portfolio. And beyond glaucoma, you think about continuing beyond U.S. glaucoma, you think about continued growth in international markets as well as the blocking and tackling of what's become a really nice business for us in the corneal health side. So I think you can paint a variety of pictures with all of that, and it's understandable. And we'll get into more detail when we have our fourth quarter call at the end of February.

Of course. So I guess, when it came to the new product side of things, I really thought I'd be entering this call talking about infinite, right, since that was expected in the first half of the year. And as I mentioned already, I think iPrime came as a little bit of a surprise last week, I believe. When people think of viscodelivery, there's probably one competitor they really think of. But when we think of having a device with this kind of profile in your own portfolio, how does it really stack up against the competition? And I would also say that it's kind of interesting to note that you specifically highlight this as a standalone device within your slide deck, right? So how should we think about the relationship between iPrime and your existing inject portfolio for mild to moderate?

Chris, do you want to take that?

I'll handle that one. First of all, we were thrilled with the FDA approval, and we're excited about the prospects of the product itself. It broadens our portfolio, gives our physicians and our customers more options. In terms of how it stacks up against competition and how we are going to approach the market, we're obviously going to take a "let's wait until we launch approach" with that. At that time, at a later time, we can get into more specifics around the advantages and the strategies that we're going to deploy.

Got it. Okay. And then moving on to infinite, right? So I feel that there are still some questions that need to be launched here, but how quickly do you really see this ramping once you do get approval? How long will it take to figure out what reimbursement will be from the max? And how large would you really size the opportunity here even before potentially, SA? And then you know if you're willing to opine on the SA opportunity, though, I wouldn't say no to that either.

Yes, I'd be happy to take that. So we think if you've seen the data today with infinite and we reiterated just how robust the pressure-lowering activity, we haven't seen this kind of mean pressure lowering activity in any other product that we've launched to date. So we're excited about how it performs even in the most difficult patients. And so that bodes well for its earlier intervention in the treatment of glaucoma provided that we can move with the FDA, get this IDE approached and be able to expand the labeling and claims. I think if we look historically, it's about a 6- to 9-month sledding process with the MAX being able to establish the professional fees and to get those to the position that we'd like them to be. And then we have some heavy sledding that we'll need to undertake to be able to move the current APC assignment that CMS has left us with, part of the debris from last year. We made so many, I think, wonderful changes and reverses at some of the initial proposed rules, but that's something that we'll need to be able to address and move forward over the course of 2022. And if we're successful, Allen, that will be available in 2023. Longer term, the ability to have a single implantation and a prosthetic that can restore natural outflow and be able to eliminate drop therapy principally for, as the data shows for several years, maybe several decades. We think it provides a phenomenal long-term opportunity for the company. When we talked about early TAMs, we're looking at 200,000 eyes as we go out, expanding into 500,000 to 600,000 with some expression and expansion of indication. And that could be far greater depending upon the appetite and how well we perform and how well the product works in these standalone patients. But there's no question that long term, I believe there'll be a paradigm change in the treatment of glaucoma using these onetime installations like the iStent infinite and the iDose device.

Yes. So continuing on that track with iDose, right? I still remember 2015, when you guys first IPO-ed, it was when I first started this job, I feel like iDose was kind of the big thing to be talking about with the story. And it is kind of exciting to be really close to that launch. But with the 2022 submission, 2023 launch, it's been a long time coming, I just want to make sure like how confident are you in that time line and really being able to hit that? It seems like Phase III is on track, but with everything that's going on with the FDA, everything going on in the world, is there any risk to that time line?

Well, I will tell you that we're on track, right? And as I mentioned in the presentation today, we're looking to file the NDA at the tail end of this year and look for approval in late course of 2023. There's no question that my appetite for the product and motivation just grows over time. I think when we look at the early introduction of DURYSTA, even with this highly limited label and some of the profound issues of endothelial cell loss, the product is doing reasonably well. And by our reckoning, over $50 million in sales in its first year. And I think what's important, too, is the predicate on pricing that they've established by having a J code that pays over $2,000 for a 3- to 4-month therapy bodes well for a product that I just showed today, maybe giving patients relief from topical drop therapy for up to 3 years. And so when we look at the TAM, the other important thing, Allen, is that this product will be regulated under an NDA, and we'll have open field running, presumably all the way for ocular hypertension to refractory glaucoma. And so we see this as a product that will have the ability to penetrate, by our reckoning, a 3 million eye -- annual eye marketplace. And so it will not happen overnight. As we said, we'll be sophisticated in how we launch. We'll pick the right power alleys of where it plays best. And I do believe this will be like Pac-Man. It will grow over time and become a principal first driver in the treatment of glaucoma therapy.

Moving on to the 2 Phase II trials that you announced today. Unfortunately, there just isn't enough time to dive into both of those opportunities as much as I would love to. But when I look at kind of the time frame for those, those are both pretty quick trials what should -- I would expect, should be pretty fast enrollment. So do you think that we should really see, especially in, say, your presbyopia trial, where it's only 20 days that we could see a turnaround in like enrollment completion before the end of the year, and maybe Phase III is starting next year. Is that a reasonable time frame to be thinking about?

Well, I think it's reasonable to argue that, right? And I think we'll need to execute and make that happen, but you said it yourself, Allen, these are acute trials that can be done rather quickly. We're going to find out our presumption that these will be successful in the treatment of dry eye and prosbiopia. And I think we will be in a prime position to begin in short order Phase III clinical trials. And I think what's important for institutional investors is that, look, this portfolio is coming alive. We talked about it. I think it's kind of been in the sleep mode for a little period of time until we'll actually be able to show executable forward-ground gain. And we have now with the enrollment in these 2 clinical trials. And make no mistake, we have many other different discovery and -- or different development programs that are on the heels of presbyopia and dry eye to expand this whole portfolio of iLution therapy.

Got it. And unfortunately, there is only -- there are only a few minutes left. I keep saying it, but I feel like there are so many things that I would love to touch on. But just when it comes to the way you spend your money, right? We've clearly seen that you've stayed pretty aggressive when it comes to bringing in these early-stage technologies that are a good fit for your existing core competencies, your existing technologies. But now, like as you highlighted in your presentation, you clearly have a lot of different shots on the goal. So should we expect to see you staying -- continue staying very active on that front? Or should we think that maybe it's time to double down on the opportunities that you have in front of you and focus on executing there?

Well, I think we're going to be cognizant of being able to put the amount of necessary resources against the programs that we already have in place and to make sure that we have the appropriate complement of resources and monies that will move those programs forward in a very expedited fashion. Having said that, you've seen how quickly we move, you can see our ambition and we are open to new assets and new technologies that can expand these paradigm-changing activities in these 3 categories that we've chosen, which are cornea, glaucoma and retinal disease.

So actually, apologies, I think I got the time a little wrong there and we do have a few more minutes to cover things. So I guess, in the time we have left, one topic that I do want to cover is international. You highlighted in your presentation that you are present in quite a few more territories now. But when I look at the performance of your international business granted, as of today, it is largely just kind of the glaucoma business. That has been impacted quite a bit of COVID-19. We've seen some challenges there. With Delta, Omicron has such a varied impact based on geography, how has internationally, specifically, fared so far into 2022? And when we do eventually get to a stable environment, hopefully, later this year, what are the main drivers that can really get that business growing again?

Chris and Joe, I'll turn it to you.

You start, Chris, and you can add color.

Yes. Yes. So clearly, we've been pleased by the continued progress we've had throughout -- prior to and throughout COVID-19 in international markets. I'll say it's been a bit like a game of whack a mole over the last 2 years, where in any given quarter, a particular part of the world has been impacted more than others as it relates to COVID-19. And so I think what we've seen is continued execution, but not a true unleashing of the potential in those markets and our business within those markets. So I think it encourages us for the setup as we think about the years to come in building that market. Historically, within ophthalmic markets, the international opportunity represents about the same size as the U.S. So when you think about the scale of our U.S. combo cataract glaucoma business, we still are in the early innings of developing our international business, both in the markets that we're in today and also some of the markets that we'll target in the years to come. So I think we continue to see blocking and tackling execution, stable reimbursement, stable pricing. And we look forward to some of the COVID-related headwinds and noise abating over the course of 2022.

I think the only thing I'll add is the success that we've achieved internationally has been very broad-based. And it continues to broaden even more with each passing quarter. So the investments that we've made since 2015, since we went -- we did our IPO are beginning to bear fruit, and we're really pleased with what's going on in international.

When I think of the portfolio that you have internationally, I guess, like should we think of that as largely being limited Epi-Off and iStent inject today. What should we think about as the time line like once you have infinite and once you have iDose, how quickly will you be aiming to really move those internationally and begin growing that as well?

I'll start out. So you're correct. Right now, it's largely W -- iStent inject W and Epi-Off or Epioxa, is our product. And that is largely what composes the international sales. Having said that, once we start getting infinite approval and Epi-On, you will see those cascade into different countries, usually a few months after, up to a year in some markets. But the U.S. will continue -- or move forward, U.S. will be the launching of those products and move quickly into the international market.

Got you. So we only have a minute or so left. So I just want to give the time to you guys. If you were to leave -- want to leave investors of 1 or 2 major things to think about going forward, what would that be?

Well, I think I would drill down and say, year 2022, we are profoundly moving towards a year of catalysts, both on the commercial side and on the regulatory side, and you can see that in the course of the presentation today. And I would emphasize as well that the 16 development programs that we've now disclosed to the investment community are starting to bloom. And you can see that with the profound traction that we're gaining, both in the pharmaceutical and medical device side. I think we're for real, we're change agents and we're here to transform vision.

Got it. Well, thank you guys so much for the time. Thank you, everyone, for listening in, and I hope you all enjoy the rest of your evenings.

Okay. Allen, thank you, Allen.

Thanks, Allen.